rs62114506

Variant names:

• chr2-242793-G-A
• rs62114506
• NM_015677.4:c.291+4745C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-242793-G-A
• chr2-242793-G-C
• chr2-242793-G-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015677.4(SH3YL1):​c.291+4745C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000145 in 1,383,798 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SH3YL1 NM_015677.4 intron
• Scores: Splicing: ADA: 0.00008660
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.243
• Publications: 21 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015677.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3YL1	NM_015677.4	MANE Select	c.291+4745C>T		intron	N/A	NP_056492.2
	SH3YL1	NM_001159597.3		c.291+4745C>T		intron	N/A	NP_001153069.1
	SH3YL1	NM_001282687.2		c.3+5C>T		splice_region intron	N/A	NP_001269616.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3YL1	ENST00000356150.10	TSL:1 MANE Select	c.291+4745C>T		intron	N/A	ENSP00000348471.5
	SH3YL1	ENST00000403712.6	TSL:1	c.291+4745C>T		intron	N/A	ENSP00000384276.1
	SH3YL1	ENST00000626873.2	TSL:5	c.3+5C>T		splice_region intron	N/A	ENSP00000485824.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000145 AC: 2 AN: 1383798 Hom.: 0 Cov.: 37 AF XY: 0.00000146 AC XY: 1 AN XY: 682596

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30990

American (AMR) AF: 0.0000302 AC: 1 AN: 33090

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24814

East Asian (EAS) AF: 0.0000291 AC: 1 AN: 34402

South Asian (SAS) AF: 0.00 AC: 0 AN: 76544

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48504

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5646

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1072472

Other (OTH) AF: 0.00 AC: 0 AN: 57336

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 1319

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.4
DANN	Benign	0.81
PhyloP100		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000087
dbscSNV1_RF	Benign	0.0
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: rs62114506; hg19: chr2-242793;