2-246301-T-A

Position:

• chr2-246301-T-A

Variant summary

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

The NM_015677.4(SH3YL1):​c.291+1237A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.913 in 152,224 control chromosomes in the GnomAD database, including 63,561 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 (63561 hom., cov: 32)
• Consequence: SH3YL1 NM_015677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.174

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.96 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3YL1	NM_015677.4	c.291+1237A>T		intron_variant		ENST00000356150.10	NP_056492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3YL1	ENST00000356150.10	c.291+1237A>T		intron_variant		1	NM_015677.4	ENSP00000348471	P1

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138859 AN: 152110 Hom.: 63505 Cov.: 32

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.891

Gnomad SAS AF: 0.921

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: 0.913 AC: 138971 AN: 152224 Hom.: 63561 Cov.: 32 AF XY: 0.910 AC XY: 67710 AN XY: 74422

Gnomad4 AFR AF: 0.968

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.891

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.843

Gnomad4 NFE AF: 0.899

Gnomad4 OTH AF: 0.906

Alfa AF: 0.913 Hom.: 7861

Bravo AF: 0.920

Asia WGS AF: 0.906 AC: 3148 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.0
DANN	Benign	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

Other links and lift over

dbSNP: rs10193882; hg19: chr2-246301;