rs300703

Positions:

• chr2-239416-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.292-5144G>A 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 152,264 control chromosomes in the GnomAD database, including 63,602 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 (63596 hom., cov: 32)
  • Exomes 𝑓: 0.93 (6 hom.)
• Consequence: SH3YL1 NM_015677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.98

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]

SH3YL1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.08).
• 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.292-5144G>A		intron_variant		ENST00000356150.10	NP_056492.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3YL1	ENST00000356150.10	c.292-5144G>A		intron_variant		1	NM_015677.4	ENSP00000348471.5
SH3YL1	ENST00000626873.2	c.3+3382G>A		intron_variant		5		ENSP00000485824.1

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138906 AN: 152132 Hom.: 63540 Cov.: 32

Gnomad AFR AF: 0.968

Gnomad AMI AF: 0.825

Gnomad AMR AF: 0.893

Gnomad ASJ AF: 0.884

Gnomad EAS AF: 0.897

Gnomad SAS AF: 0.921

Gnomad FIN AF: 0.844

Gnomad MID AF: 0.908

Gnomad NFE AF: 0.899

Gnomad OTH AF: 0.906

GnomAD4 exome AF: 0.929 AC: 13 AN: 14 Hom.: 6 AF XY: 1.00 AC XY: 10 AN XY: 10

Gnomad4 AMR exome AF: 1.00

Gnomad4 ASJ exome AF: 1.00

Gnomad4 NFE exome AF: 0.833

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.913 AC: 139019 AN: 152250 Hom.: 63596 Cov.: 32 AF XY: 0.910 AC XY: 67742 AN XY: 74440

Gnomad4 AFR AF: 0.968

Gnomad4 AMR AF: 0.893

Gnomad4 ASJ AF: 0.884

Gnomad4 EAS AF: 0.897

Gnomad4 SAS AF: 0.920

Gnomad4 FIN AF: 0.844

Gnomad4 NFE AF: 0.899

Gnomad4 OTH AF: 0.905

Alfa AF: 0.916 Hom.: 11788

Bravo AF: 0.920

Asia WGS AF: 0.911 AC: 3164 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.34
DANN	Benign	0.66

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: rs300703; hg19: chr2-239416;