2-259296-C-G

Variant names:

• chr2-259296-C-G
• rs4255987
• NM_015677.4:c.1+4688G>C

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+4688G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 152,100 control chromosomes in the GnomAD database, including 7,498 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 0.30 (7498 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SH3YL1 NM_015677.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.258
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SH3YL1	NM_015677.4	c.1+4688G>C		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+4688G>C		intron_variant	Intron 1 of 9	1	NM_015677.4	ENSP00000348471.5
SH3YL1	ENST00000626873.2	c.-555-2956G>C		intron_variant	Intron 1 of 12	5		ENSP00000485824.1

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45551 AN: 151982 Hom.: 7504 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.257

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.327

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.397

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.344

Gnomad OTH AF: 0.301

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.299 AC: 45547 AN: 152100 Hom.: 7498 Cov.: 32 AF XY: 0.302 AC XY: 22474 AN XY: 74340

African (AFR) AF: 0.178 AC: 7403 AN: 41528

American (AMR) AF: 0.269 AC: 4112 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.327 AC: 1134 AN: 3472

East Asian (EAS) AF: 0.592 AC: 3053 AN: 5160

South Asian (SAS) AF: 0.273 AC: 1317 AN: 4828

European-Finnish (FIN) AF: 0.397 AC: 4192 AN: 10552

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23364 AN: 67954

Other (OTH) AF: 0.301 AC: 637 AN: 2114

Alfa AF: 0.196 Hom.: 443

Bravo AF: 0.287

Asia WGS AF: 0.367 AC: 1276 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.52
PhyloP100		0.26
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: rs4255987; hg19: chr2-259296;