2-256278-T-C

Variant summary

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

The NM_015677.4(SH3YL1):c.2-3163A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 152,238 control chromosomes in the GnomAD database, including 6,802 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 0.27 (6801 hom., cov: 33)
  • Exomes 𝑓: 0.40 (1 hom.)
• Consequence: SH3YL1 NM_015677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423

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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SH3YL1	NM_015677.4	c.2-3163A>G		intron_variant		ENST00000356150.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SH3YL1	ENST00000356150.10	c.2-3163A>G		intron_variant		1	NM_015677.4	P1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41732 AN: 152110 Hom.: 6808 Cov.: 33

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.281

GnomAD4 exome AF: 0.400 AC: 4 AN: 10 Hom.: 1 Cov.: 0 AF XY: 0.333 AC XY: 2 AN XY: 6

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.274 AC: 41715 AN: 152228 Hom.: 6801 Cov.: 33 AF XY: 0.277 AC XY: 20598 AN XY: 74422

Gnomad4 AFR AF: 0.0980

Gnomad4 AMR AF: 0.262

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.527

Gnomad4 SAS AF: 0.258

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.344

Gnomad4 OTH AF: 0.279

Alfa AF: 0.300 Hom.: 4115

Bravo AF: 0.258

Asia WGS AF: 0.319 AC: 1108 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	1.2
Dann	Benign	0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs4455191; hg19: chr2-256278;