rs1483435746

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 2P and 11B. PM2BP4_ModerateBP6_Very_StrongBP7

The NM_016169.4(SUFU):c.96G>A(p.Pro32Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000346 in 1,446,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. P32P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000069 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000031 ( 0 hom. )

Consequence

SUFU
NM_016169.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.09

Publications

1 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 -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.4).

BP6

Variant 10-102504248-G-A is Benign according to our data. Variant chr10-102504248-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 940162.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.09 with no splicing effect.

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.96G>A	p.Pro32Pro	synonymous	Exon 1 of 12	NP_057253.2
	SUFU	NM_001178133.2		c.96G>A	p.Pro32Pro	synonymous	Exon 1 of 11	NP_001171604.1	Q9UMX1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SUFU	ENST00000369902.8	TSL:1 MANE Select	c.96G>A	p.Pro32Pro	synonymous	Exon 1 of 12	ENSP00000358918.4	Q9UMX1-1
SUFU	ENST00000423559.2	TSL:1	c.96G>A	p.Pro32Pro	synonymous	Exon 1 of 10	ENSP00000411597.2	Q9UMX1-3
SUFU	ENST00000369899.6	TSL:1	c.96G>A	p.Pro32Pro	synonymous	Exon 1 of 11	ENSP00000358915.2	Q9UMX1-2

Frequencies

GnomAD3 genomes

AF:

0.00000689

AC:

AN:

145214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000150

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000811

AC:

AN:

246562

AF XY:

0.0000149

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000307

AC:

AN:

1301406

Hom.:

Cov.:

AF XY:

0.00000309

AC XY:

AN XY:

646390

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

28248

American (AMR)

AF:

0.00

AC:

AN:

39512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20276

East Asian (EAS)

AF:

0.00

AC:

AN:

27898

South Asian (SAS)

AF:

0.00

AC:

AN:

84692

European-Finnish (FIN)

AF:

0.00

AC:

AN:

36672

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4918

European-Non Finnish (NFE)

AF:

0.00000297

AC:

AN:

1009690

Other (OTH)

AF:

0.0000202

AC:

AN:

49500

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000689

AC:

AN:

145214

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

70698

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39702

American (AMR)

AF:

0.00

AC:

AN:

14596

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3410

East Asian (EAS)

AF:

0.00

AC:

AN:

4312

South Asian (SAS)

AF:

0.00

AC:

AN:

3998

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9512

Middle Eastern (MID)

AF:

0.00

AC:

AN:

312

European-Non Finnish (NFE)

AF:

0.0000150

AC:

AN:

66446

Other (OTH)

AF:

0.00

AC:

AN:

2044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Gorlin syndrome;C0025149:Medulloblastoma (1)

Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.40

CADD

Benign

(source)

DANN

Uncertain

0.98

PhyloP100

1.1

PromoterAI

0.046

Neutral

(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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over