Genetic Variant SH3YL1:p.Val141Leu (chr2-233213-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015677.4(SH3YL1):c.421G>C(p.Val141Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000703 in 1,421,514 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V141M) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

SH3YL1
NM_015677.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.26

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22351038).

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.421G>C	p.Val141Leu	missense	Exon 6 of 10	NP_056492.2	Q96HL8-1
SH3YL1	NM_001159597.3		c.421G>C	p.Val141Leu	missense	Exon 6 of 9	NP_001153069.1	Q96HL8-2
SH3YL1	NM_001282687.2		c.133G>C	p.Val45Leu	missense	Exon 8 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.421G>C	p.Val141Leu	missense	Exon 6 of 10	ENSP00000348471.5	Q96HL8-1
SH3YL1	ENST00000403712.6	TSL:1	c.421G>C	p.Val141Leu	missense	Exon 6 of 9	ENSP00000384276.1	Q96HL8-2
SH3YL1	ENST00000626873.2	TSL:5	c.133G>C	p.Val45Leu	missense	Exon 9 of 13	ENSP00000485824.1	Q96HL8-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.03e-7

AC:

AN:

1421514

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

706562

show subpopulations

African (AFR)

AF:

0.0000310

AC:

AN:

32226

American (AMR)

AF:

0.00

AC:

AN:

38888

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24922

East Asian (EAS)

AF:

0.00

AC:

AN:

38774

South Asian (SAS)

AF:

0.00

AC:

AN:

80072

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52094

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5590

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1090712

Other (OTH)

AF:

0.00

AC:

AN:

58236

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

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.11

Eigen

Benign

-0.40

Eigen_PC

Benign

-0.37

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.97

M_CAP

Benign

0.026

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

PhyloP100

3.3

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-1.4

REVEL

Benign

0.070

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.028

Polyphen

0.085

Vest4

0.42

MutPred

0.52

Loss of helix (P = 0.0196)

MVP

0.17

MPC

0.16

ClinPred

0.78

GERP RS

3.9

Varity_R

0.29

gMVP

0.73

Mutation Taster

=71/29

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over