dbSNP rs968837112: SH3YL1:p.Ala200Ser (chr2-231127-C-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_015677.4(SH3YL1):c.598G>T(p.Ala200Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A200T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SH3YL1
NM_015677.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.56

Publications

0 publications found

Variant links:

Genes affected

SH3YL1 (HGNC:29546): (SH3 and SYLF domain containing 1) Enables phosphatase binding activity and phosphatidylinositol binding activity. Predicted to act upstream of or within phosphatidylinositol biosynthetic process and regulation of ruffle assembly. Located in ruffle membrane. [provided by Alliance of Genome Resources, Apr 2022]

SH3YL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3YL1	NM_015677.4	MANE Select	c.598G>T	p.Ala200Ser	missense	Exon 7 of 10	NP_056492.2	Q96HL8-1
SH3YL1	NM_001159597.3		c.598G>T	p.Ala200Ser	missense	Exon 7 of 9	NP_001153069.1	Q96HL8-2
SH3YL1	NM_001282687.2		c.310G>T	p.Ala104Ser	missense	Exon 9 of 12	NP_001269616.1	Q96HL8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3YL1	ENST00000356150.10	TSL:1 MANE Select	c.598G>T	p.Ala200Ser	missense	Exon 7 of 10	ENSP00000348471.5	Q96HL8-1
SH3YL1	ENST00000403712.6	TSL:1	c.598G>T	p.Ala200Ser	missense	Exon 7 of 9	ENSP00000384276.1	Q96HL8-2
SH3YL1	ENST00000626873.2	TSL:5	c.310G>T	p.Ala104Ser	missense	Exon 10 of 13	ENSP00000485824.1	Q96HL8-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461778

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727200

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33476

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39688

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111930

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.099

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.82

M_CAP

Benign

0.014

MetaRNN

Uncertain

0.50

MetaSVM

Benign

-0.69

MutationAssessor

Pathogenic

2.9

PhyloP100

3.6

PrimateAI

Benign

0.43

PROVEAN

Benign

-2.3

REVEL

Benign

0.20

Sift

Uncertain

0.023

Sift4G

Benign

0.067

Polyphen

0.94

Vest4

0.29

MutPred

0.53

Gain of disorder (P = 0.0732)

MVP

0.46

MPC

0.17

ClinPred

0.92

GERP RS

5.1

Varity_R

0.16

gMVP

0.63

Mutation Taster

=86/14

polymorphism

(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

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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