2-252197-C-T

Variant names:

• chr2-252197-C-T
• rs4241316
• NM_015677.4:c.112+808G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SH3YL1	NM_015677.4	c.112+808G>A		intron_variant	Intron 2 of 9	ENST00000356150.10	NP_056492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3YL1	ENST00000356150.10	c.112+808G>A		intron_variant	Intron 2 of 9	1	NM_015677.4	ENSP00000348471.5
SH3YL1	ENST00000626873.2	c.-311+808G>A		intron_variant	Intron 3 of 12	5		ENSP00000485824.1

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

African (AFR) AF: 0.964 AC: 40062 AN: 41578

American (AMR) AF: 0.893 AC: 13663 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3071 AN: 3472

East Asian (EAS) AF: 0.891 AC: 4621 AN: 5188

South Asian (SAS) AF: 0.919 AC: 4437 AN: 4826

European-Finnish (FIN) AF: 0.843 AC: 8934 AN: 10600

Middle Eastern (MID) AF: 0.908 AC: 267 AN: 294

European-Non Finnish (NFE) AF: 0.899 AC: 61162 AN: 68034

Other (OTH) AF: 0.906 AC: 1912 AN: 2110

Alfa AF: 0.907 Hom.: 100171

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
PhyloP100		0.039
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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