rs12414407

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_016169.4(SUFU):c.1365+19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 1,609,952 control chromosomes in the GnomAD database, including 346,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35758 hom., cov: 34)

Exomes 𝑓: 0.65 ( 310627 hom. )

Consequence

SUFU
NM_016169.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.452

Publications

31 publications found

Variant links:

Genes affected

SUFU (HGNC:16466): (SUFU negative regulator of hedgehog signaling) The Hedgehog signaling pathway plays an important role in early human development. The pathway is a signaling cascade that plays a role in pattern formation and cellular proliferation during development. This gene encodes a negative regulator of the hedgehog signaling pathway. Defects in this gene are a cause of medulloblastoma. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

SUFU Gene-Disease associations (from GenCC):

medulloblastoma
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
nevoid basal cell carcinoma syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Illumina, Genomics England PanelApp
basal cell nevus syndrome 2
Inheritance: AD Classification: STRONG Submitted by: G2P
ocular motor apraxia, Cogan type
Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox
Joubert syndrome 32
Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
Joubert syndrome
Inheritance: AR, AD Classification: MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics
apraxia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
ciliopathy
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

SUFU links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 10-102627262-T-C is Benign according to our data. Variant chr10-102627262-T-C is described in ClinVar as Benign. ClinVar VariationId is 260688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SUFU	NM_016169.4 link	c.1365+19T>C		intron_variant	Intron 11 of 11	ENST00000369902.8	NP_057253.2	Q9UMX1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SUFU	ENST00000369902.8 link	c.1365+19T>C		intron_variant	Intron 11 of 11	1	NM_016169.4	ENSP00000358918.4		Q9UMX1-1

Frequencies

GnomAD3 genomes

AF:

0.683

AC:

103853

AN:

152102

Hom.:

35723

Cov.:

show subpopulations

Gnomad AFR

AF:

0.752

Gnomad AMI

AF:

0.599

Gnomad AMR

AF:

0.634

Gnomad ASJ

AF:

0.701

Gnomad EAS

AF:

0.748

Gnomad SAS

AF:

0.711

Gnomad FIN

AF:

0.607

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.656

Gnomad OTH

AF:

0.702

GnomAD2 exomes

AF:

0.659

AC:

165628

AN:

251454

AF XY:

0.662

show subpopulations

Gnomad AFR exome

AF:

0.754

Gnomad AMR exome

AF:

0.578

Gnomad ASJ exome

AF:

0.689

Gnomad EAS exome

AF:

0.745

Gnomad FIN exome

AF:

0.609

Gnomad NFE exome

AF:

0.647

Gnomad OTH exome

AF:

0.659

GnomAD4 exome

AF:

0.651

AC:

949428

AN:

1457730

Hom.:

310627

Cov.:

AF XY:

0.654

AC XY:

474177

AN XY:

725372

show subpopulations

African (AFR)

AF:

0.760

AC:

25394

AN:

33408

American (AMR)

AF:

0.587

AC:

26251

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.689

AC:

17981

AN:

26102

East Asian (EAS)

AF:

0.720

AC:

28561

AN:

39670

South Asian (SAS)

AF:

0.712

AC:

61364

AN:

86158

European-Finnish (FIN)

AF:

0.613

AC:

32696

AN:

53380

Middle Eastern (MID)

AF:

0.702

AC:

4045

AN:

5760

European-Non Finnish (NFE)

AF:

0.643

AC:

712752

AN:

1108280

Other (OTH)

AF:

0.670

AC:

40384

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

15980

31960

47941

63921

79901

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18776

37552

56328

75104

93880

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.683

AC:

103944

AN:

152222

Hom.:

35758

Cov.:

AF XY:

0.680

AC XY:

50603

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.752

AC:

31256

AN:

41540

American (AMR)

AF:

0.633

AC:

9688

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.701

AC:

2433

AN:

3470

East Asian (EAS)

AF:

0.747

AC:

3877

AN:

5190

South Asian (SAS)

AF:

0.711

AC:

3438

AN:

4834

European-Finnish (FIN)

AF:

0.607

AC:

6428

AN:

10584

Middle Eastern (MID)

AF:

0.701

AC:

206

AN:

294

European-Non Finnish (NFE)

AF:

0.656

AC:

44585

AN:

67994

Other (OTH)

AF:

0.705

AC:

1490

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1768

3536

5304

7072

8840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

828

1656

2484

3312

4140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.661

Hom.:

27583

Bravo

AF:

0.685

Asia WGS

AF:

0.716

AC:

2487

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 26, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: The SUFU c.1365+19T>C variant involves the alteration of a non-conserved intronic nucleotide. Mutation taster predicts the variant to be neutral along with 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 80437/121368 control chromosomes (including 26892 homozygotes) at a frequency of 0.6627529, indicating the variant to be the ancestral allele and a common benign polymorphism. Taken together, this variant is classified as Benign. -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Joubert syndrome 32

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Gorlin syndrome

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Gorlin syndrome;C0025149:Medulloblastoma

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Familial meningioma

Benign:1

Jul 07, 2023

KCCC/NGS Laboratory, Kuwait Cancer Control Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

7.0

(source)

DANN

Benign

0.60

PhyloP100

0.45

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over