2-252197-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015677.4(SH3YL1):c.112+808G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.912 in 152,314 control chromosomes in the GnomAD database, including 63,429 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.91 (63429 hom., cov: 33)
• Consequence: SH3YL1 NM_015677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0390

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3YL1	NM_015677.4	c.112+808G>A		intron_variant		ENST00000356150.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3YL1	ENST00000356150.10	c.112+808G>A		intron_variant		1	NM_015677.4	P1

Frequencies

GnomAD3 genomes AF: 0.912 AC: 138771 AN: 152196 Hom.: 63377 Cov.: 33

Gnomad AFR AF: 0.964

Gnomad AMI AF: 0.823

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.885

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.920

Gnomad FIN AF: 0.843

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.907

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.912 AC: 138880 AN: 152314 Hom.: 63429 Cov.: 33 AF XY: 0.909 AC XY: 67662 AN XY: 74472

Gnomad4 AFR AF: 0.964

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.885

Gnomad4 EAS AF: 0.891

Gnomad4 SAS AF: 0.919

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.899

Gnomad4 OTH AF: 0.906

Alfa AF: 0.905 Hom.: 68873

Bravo AF: 0.919

Asia WGS AF: 0.905 AC: 3144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.1
Dann	Benign	0.41

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: rs4241316; hg19: chr2-252197; COSMIC: COSV62158004; COSMIC: COSV62158004;