chr2-231139-G-A

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015677.4(SH3YL1):​c.586C>T​(p.Arg196Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000341 in 1,613,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000029 ( 0 hom. )

Consequence

SH3YL1
NM_015677.4 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.0840399).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SH3YL1NM_015677.4 linkuse as main transcriptc.586C>T p.Arg196Trp missense_variant 7/10 ENST00000356150.10 NP_056492.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SH3YL1ENST00000356150.10 linkuse as main transcriptc.586C>T p.Arg196Trp missense_variant 7/101 NM_015677.4 ENSP00000348471 P1Q96HL8-1

Frequencies

GnomAD3 genomes
AF:
0.0000855
AC:
13
AN:
152110
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000576
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000762
AC:
19
AN:
249412
Hom.:
0
AF XY:
0.0000591
AC XY:
8
AN XY:
135352
show subpopulations
Gnomad AFR exome
AF:
0.000258
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000501
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000530
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000287
AC:
42
AN:
1461622
Hom.:
0
Cov.:
30
AF XY:
0.0000220
AC XY:
16
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000202
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000261
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152228
Hom.:
0
Cov.:
33
AF XY:
0.000148
AC XY:
11
AN XY:
74452
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000165
Hom.:
0
Bravo
AF:
0.000106
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.00
AC:
0
ExAC
AF:
0.0000828
AC:
10
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 03, 2023The c.586C>T (p.R196W) alteration is located in exon 7 (coding exon 7) of the SH3YL1 gene. This alteration results from a C to T substitution at nucleotide position 586, causing the arginine (R) at amino acid position 196 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.41
CADD
Pathogenic
27
DANN
Uncertain
1.0
DEOGEN2
Benign
0.11
.;.;.;T;T;.;T;T
Eigen
Benign
0.16
Eigen_PC
Benign
0.081
FATHMM_MKL
Benign
0.69
D
LIST_S2
Uncertain
0.96
D;D;.;.;D;D;D;D
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.084
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.5
L;.;.;L;L;.;.;.
MutationTaster
Benign
1.0
N;N;N
PrimateAI
Benign
0.23
T
PROVEAN
Benign
-2.1
N;.;N;N;N;N;N;N
REVEL
Benign
0.14
Sift
Uncertain
0.0060
D;.;D;D;D;D;T;D
Sift4G
Uncertain
0.021
.;D;D;.;.;D;D;D
Polyphen
0.96
D;D;D;D;D;D;.;.
Vest4
0.44
MVP
0.46
MPC
0.34
ClinPred
0.13
T
GERP RS
5.0
Varity_R
0.082
gMVP
0.68

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs560342993; hg19: chr2-231139; COSMIC: COSV62155490; COSMIC: COSV62155490; API