2-218902-A-T

Variant names:

• chr2-218902-A-T
• rs889971539
• NM_015677.4:c.938T>A

Variant summary

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

The NM_015677.4(SH3YL1):​c.938T>A​(p.Ile313Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SH3YL1 NM_015677.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.609

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]

ACMG classification

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 rank	MANE	Protein	UniProt
SH3YL1	NM_015677.4	c.938T>A	p.Ile313Lys	missense_variant	Exon 10 of 10	ENST00000356150.10	NP_056492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3YL1	ENST00000356150.10	c.938T>A	p.Ile313Lys	missense_variant	Exon 10 of 10	1	NM_015677.4	ENSP00000348471.5
SH3YL1	ENST00000626873.2	c.650T>A	p.Ile217Lys	missense_variant	Exon 13 of 13	5		ENSP00000485824.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.050	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	16
DANN	Benign	0.86
DEOGEN2	Benign	0.15	.;.;.;T;T;.;T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.085	N
LIST_S2	Uncertain	0.89	D;D;.;.;D;D;D
M_CAP	Benign	0.077	D
MetaRNN	Uncertain	0.45	T;T;T;T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	2.0	.;.;.;M;M;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-4.2	D;.;D;D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0090	D;.;D;D;D;D;D
Sift4G	Uncertain	0.021	.;D;D;.;.;D;D
Polyphen		0.21	B;B;P;B;B;P;.
Vest4		0.33
MutPred		0.82		.;.;.;Gain of disorder (P = 0.0018);Gain of disorder (P = 0.0018);.;.;
MVP		0.45
MPC		0.15
ClinPred		0.50	D
GERP RS		-2.1
Varity_R		0.54
gMVP		0.87

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

Other links and lift over

dbSNP: rs889971539; hg19: chr2-218902;