rs10167992

Variant names:

• chr2-263270-T-C
• rs10167992
• NM_015677.4:c.1+714A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015677.4(SH3YL1):​c.1+714A>G 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 154,280 control chromosomes in the GnomAD database, including 64,421 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 (63580 hom., cov: 33)
  • Exomes 𝑓: 0.90 (841 hom.)
• Consequence: SH3YL1 NM_015677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906
• Publications: 14 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=-0.9).
• 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 rank	MANE	Protein	UniProt
SH3YL1	NM_015677.4	c.1+714A>G		intron_variant	Intron 1 of 9	ENST00000356150.10	NP_056492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SH3YL1	ENST00000356150.10	c.1+714A>G		intron_variant	Intron 1 of 9	1	NM_015677.4	ENSP00000348471.5
SH3YL1	ENST00000626873.2	c.-556+874A>G		intron_variant	Intron 1 of 12	5		ENSP00000485824.1

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138888 AN: 152104 Hom.: 63528 Cov.: 33

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.826

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.885

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

GnomAD4 exome AF: 0.905 AC: 1862 AN: 2058 Hom.: 841 Cov.: 0 AF XY: 0.901 AC XY: 1033 AN XY: 1146

African (AFR) AF: 0.900 AC: 18 AN: 20

American (AMR) AF: 0.902 AC: 305 AN: 338

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2

East Asian (EAS) AF: 0.850 AC: 34 AN: 40

South Asian (SAS) AF: 0.930 AC: 132 AN: 142

European-Finnish (FIN) AF: 0.800 AC: 24 AN: 30

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.907 AC: 1282 AN: 1414

Other (OTH) AF: 0.931 AC: 67 AN: 72

GnomAD4 genome AF: 0.913 AC: 138997 AN: 152222 Hom.: 63580 Cov.: 33 AF XY: 0.910 AC XY: 67701 AN XY: 74406

African (AFR) AF: 0.968 AC: 40199 AN: 41544

American (AMR) AF: 0.893 AC: 13659 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.885 AC: 3071 AN: 3470

East Asian (EAS) AF: 0.890 AC: 4607 AN: 5174

South Asian (SAS) AF: 0.920 AC: 4442 AN: 4830

European-Finnish (FIN) AF: 0.843 AC: 8925 AN: 10582

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

European-Non Finnish (NFE) AF: 0.899 AC: 61160 AN: 68012

Other (OTH) AF: 0.906 AC: 1917 AN: 2116

Alfa AF: 0.908 Hom.: 77660

Bravo AF: 0.920

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	-0.90
CADD	Benign	0.69
DANN	Benign	0.47
PhyloP100		-0.91
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: rs10167992; hg19: chr2-263270;