rs17114803

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_016169.4(SUFU):c.1299T>C(p.Ile433Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 1,613,514 control chromosomes in the GnomAD database, including 15,918 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2263 hom., cov: 32)

Exomes 𝑓: 0.11 ( 13655 hom. )

Consequence

SUFU
NM_016169.4 splice_region, synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: 0.661

Publications

38 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae)
nevoid basal cell carcinoma syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Illumina, Genomics England PanelApp, Orphanet
basal cell nevus syndrome 2
Inheritance: AD Classification: STRONG Submitted by: G2P
neurodevelopmental disorder
Inheritance: AD Classification: STRONG Submitted by: PanelApp Australia
ocular motor apraxia, Cogan type
Inheritance: AD Classification: STRONG Submitted by: Franklin by Genoox
Joubert syndrome 32
Inheritance: AR Classification: STRONG, LIMITED Submitted by: G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
Joubert syndrome
Inheritance: AD, AR Classification: MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet
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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 10-102627177-T-C is Benign according to our data. Variant chr10-102627177-T-C is described in ClinVar as Benign. ClinVar VariationId is 260687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.661 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016169.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SUFU	NM_016169.4	MANE Select	c.1299T>C	p.Ile433Ile	splice_region synonymous	Exon 11 of 12	NP_057253.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUFU	ENST00000369902.8	TSL:1 MANE Select	c.1299T>C	p.Ile433Ile	splice_region synonymous	Exon 11 of 12	ENSP00000358918.4	Q9UMX1-1
SUFU	ENST00000929518.1		c.1428T>C	p.Ile476Ile	splice_region synonymous	Exon 12 of 13	ENSP00000599577.1
SUFU	ENST00000893176.1		c.1425T>C	p.Ile475Ile	splice_region synonymous	Exon 12 of 13	ENSP00000563235.1

Frequencies

GnomAD3 genomes

AF:

0.151

AC:

23040

AN:

152144

Hom.:

2255

Cov.:

show subpopulations

Gnomad AFR

AF:

0.219

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.193

Gnomad ASJ

AF:

0.0643

Gnomad EAS

AF:

0.416

Gnomad SAS

AF:

0.222

Gnomad FIN

AF:

0.0725

Gnomad MID

AF:

0.0823

Gnomad NFE

AF:

0.0931

Gnomad OTH

AF:

0.163

GnomAD2 exomes

AF:

0.160

AC:

40291

AN:

251478

AF XY:

0.155

show subpopulations

Gnomad AFR exome

AF:

0.224

Gnomad AMR exome

AF:

0.267

Gnomad ASJ exome

AF:

0.0715

Gnomad EAS exome

AF:

0.413

Gnomad FIN exome

AF:

0.0745

Gnomad NFE exome

AF:

0.0863

Gnomad OTH exome

AF:

0.124

GnomAD4 exome

AF:

0.111

AC:

161590

AN:

1461254

Hom.:

13655

Cov.:

AF XY:

0.113

AC XY:

82193

AN XY:

726982

show subpopulations

African (AFR)

AF:

0.221

AC:

7384

AN:

33448

American (AMR)

AF:

0.261

AC:

11682

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0679

AC:

1775

AN:

26136

East Asian (EAS)

AF:

0.447

AC:

17727

AN:

39694

South Asian (SAS)

AF:

0.226

AC:

19495

AN:

86228

European-Finnish (FIN)

AF:

0.0753

AC:

4021

AN:

53398

Middle Eastern (MID)

AF:

0.112

AC:

644

AN:

5766

European-Non Finnish (NFE)

AF:

0.0823

AC:

91433

AN:

1111496

Other (OTH)

AF:

0.123

AC:

7429

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

7304

14609

21913

29218

36522

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3740

7480

11220

14960

18700

<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:

0.152

AC:

23084

AN:

152260

Hom.:

2263

Cov.:

AF XY:

0.154

AC XY:

11484

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.219

AC:

9079

AN:

41550

American (AMR)

AF:

0.194

AC:

2967

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0643

AC:

223

AN:

3470

East Asian (EAS)

AF:

0.416

AC:

2153

AN:

5174

South Asian (SAS)

AF:

0.222

AC:

1072

AN:

4824

European-Finnish (FIN)

AF:

0.0725

AC:

769

AN:

10614

Middle Eastern (MID)

AF:

0.0850

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0931

AC:

6334

AN:

68020

Other (OTH)

AF:

0.166

AC:

351

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

996

1992

2988

3984

4980

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.116

Hom.:

4526

Bravo

AF:

0.166

Asia WGS

AF:

0.314

AC:

1086

AN:

3478

EpiCase

AF:

0.0887

EpiControl

AF:

0.0870

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Hereditary cancer-predisposing syndrome (2)

Familial meningioma (1)

Gorlin syndrome;C0025149:Medulloblastoma (1)

Medulloblastoma (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

0.66

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over