chr2-231124-C-T

Position:

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_015677.4(SH3YL1):​c.601G>A​(p.Glu201Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,613,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000042 ( 0 hom. )

Consequence

SH3YL1
NM_015677.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.880
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 Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.053268135).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SH3YL1NM_015677.4 linkuse as main transcriptc.601G>A p.Glu201Lys 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.601G>A p.Glu201Lys missense_variant 7/101 NM_015677.4 ENSP00000348471 P1Q96HL8-1

Frequencies

GnomAD3 genomes
AF:
0.000138
AC:
21
AN:
152146
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000681
AC:
17
AN:
249466
Hom.:
0
AF XY:
0.0000443
AC XY:
6
AN XY:
135374
show subpopulations
Gnomad AFR exome
AF:
0.000517
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000353
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000424
AC:
62
AN:
1461746
Hom.:
0
Cov.:
31
AF XY:
0.0000371
AC XY:
27
AN XY:
727176
show subpopulations
Gnomad4 AFR exome
AF:
0.000568
Gnomad4 AMR exome
AF:
0.000134
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000198
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000138
AC:
21
AN:
152146
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.000483
Gnomad4 AMR
AF:
0.0000654
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000823
Hom.:
0
Bravo
AF:
0.000136
ESP6500AA
AF:
0.00107
AC:
4
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000828
AC:
10

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 29, 2024The c.601G>A (p.E201K) alteration is located in exon 7 (coding exon 7) of the SH3YL1 gene. This alteration results from a G to A substitution at nucleotide position 601, causing the glutamic acid (E) at amino acid position 201 to be replaced by a lysine (K). 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
0.072
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Benign
0.093
.;.;.;T;T;.;T;T
Eigen
Benign
-0.37
Eigen_PC
Benign
-0.24
FATHMM_MKL
Benign
0.63
D
LIST_S2
Uncertain
0.90
D;D;.;.;D;D;D;D
M_CAP
Benign
0.0056
T
MetaRNN
Benign
0.053
T;T;T;T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.86
L;.;.;L;L;.;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.47
T
PROVEAN
Benign
-1.9
N;.;N;N;N;N;N;N
REVEL
Benign
0.15
Sift
Benign
0.20
T;.;T;T;T;T;T;T
Sift4G
Benign
0.23
.;T;T;.;.;T;T;T
Polyphen
0.031
B;B;B;B;B;B;.;.
Vest4
0.33
MVP
0.19
MPC
0.091
ClinPred
0.028
T
GERP RS
5.1
Varity_R
0.16
gMVP
0.52

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: rs372248085; hg19: chr2-231124; COSMIC: COSV62155415; COSMIC: COSV62155415; API