chr2-231127-C-T

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015677.4(SH3YL1):​c.598G>A​(p.Ala200Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,976 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

SH3YL1
NM_015677.4 missense

Scores

2
8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.56
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SH3YL1NM_015677.4 linkuse as main transcriptc.598G>A p.Ala200Thr 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.598G>A p.Ala200Thr missense_variant 7/101 NM_015677.4 ENSP00000348471 P1Q96HL8-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152198
Hom.:
0
Cov.:
33
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000616
AC:
9
AN:
1461778
Hom.:
0
Cov.:
30
AF XY:
0.00000825
AC XY:
6
AN XY:
727200
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152198
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113

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 GeneticsFeb 17, 2022The c.598G>A (p.A200T) 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 598, causing the alanine (A) at amino acid position 200 to be replaced by a threonine (T). 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
0.11
BayesDel_addAF
Benign
-0.065
T
BayesDel_noAF
Benign
-0.33
CADD
Uncertain
26
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.33
.;.;.;T;T;.;T;T
Eigen
Uncertain
0.61
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.90
D;D;.;.;D;D;D;D
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.57
D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.64
T
MutationAssessor
Pathogenic
3.1
M;.;.;M;M;.;.;.
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Benign
0.46
T
PROVEAN
Uncertain
-3.0
D;.;D;D;D;D;D;N
REVEL
Benign
0.21
Sift
Uncertain
0.011
D;.;D;D;D;D;T;D
Sift4G
Uncertain
0.016
.;D;D;.;.;D;D;D
Polyphen
0.97
D;D;D;D;D;D;.;.
Vest4
0.53
MutPred
0.58
Gain of phosphorylation at A200 (P = 0.021);.;.;Gain of phosphorylation at A200 (P = 0.021);Gain of phosphorylation at A200 (P = 0.021);.;.;.;
MVP
0.53
MPC
0.37
ClinPred
0.98
D
GERP RS
5.1
Varity_R
0.23
gMVP
0.73

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: rs968837112; hg19: chr2-231127; API