2-242793-G-C

Variant names:

• chr2-242793-G-C
• rs62114506
• NM_015677.4:c.291+4745C>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.291+4745C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.256 in 1,533,988 control chromosomes in the GnomAD database, including 51,992 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 0.23 (4378 hom., cov: 33)
  • Exomes 𝑓: 0.26 (47614 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

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>G		intron	N/A	NP_056492.2
	SH3YL1	NM_001159597.3		c.291+4745C>G		intron	N/A	NP_001153069.1
	SH3YL1	NM_001282687.2		c.3+5C>G		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>G		intron	N/A	ENSP00000348471.5
	SH3YL1	ENST00000403712.6	TSL:1	c.291+4745C>G		intron	N/A	ENSP00000384276.1
	SH3YL1	ENST00000626873.2	TSL:5	c.3+5C>G		splice_region intron	N/A	ENSP00000485824.1

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35205 AN: 151884 Hom.: 4380 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.201

Gnomad ASJ AF: 0.230

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.329

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.201

GnomAD2 exomes AF: 0.247 AC: 34148 AN: 138376 AF XY: 0.251

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.198

Gnomad ASJ exome AF: 0.224

Gnomad EAS exome AF: 0.218

Gnomad FIN exome AF: 0.328

Gnomad NFE exome AF: 0.255

Gnomad OTH exome AF: 0.235

GnomAD4 exome AF: 0.259 AC: 357661 AN: 1381986 Hom.: 47614 Cov.: 37 AF XY: 0.260 AC XY: 177288 AN XY: 681612

African (AFR) AF: 0.139 AC: 4303 AN: 30940

American (AMR) AF: 0.199 AC: 6550 AN: 32964

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 5580 AN: 24782

East Asian (EAS) AF: 0.206 AC: 7076 AN: 34360

South Asian (SAS) AF: 0.287 AC: 21854 AN: 76114

European-Finnish (FIN) AF: 0.324 AC: 15705 AN: 48434

Middle Eastern (MID) AF: 0.223 AC: 1256 AN: 5634

European-Non Finnish (NFE) AF: 0.262 AC: 281232 AN: 1071496

Other (OTH) AF: 0.246 AC: 14105 AN: 57262

GnomAD4 genome AF: 0.232 AC: 35205 AN: 152002 Hom.: 4378 Cov.: 33 AF XY: 0.235 AC XY: 17469 AN XY: 74300

African (AFR) AF: 0.153 AC: 6326 AN: 41460

American (AMR) AF: 0.200 AC: 3064 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.230 AC: 797 AN: 3472

East Asian (EAS) AF: 0.225 AC: 1161 AN: 5162

South Asian (SAS) AF: 0.276 AC: 1328 AN: 4812

European-Finnish (FIN) AF: 0.329 AC: 3470 AN: 10556

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18190 AN: 67936

Other (OTH) AF: 0.199 AC: 419 AN: 2110

Alfa AF: 0.219 Hom.: 1319

Bravo AF: 0.215

Asia WGS AF: 0.255 AC: 891 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.87
PhyloP100		0.24
Mutation Taster		=47/53	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000087
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.22		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs62114506; hg19: chr2-242793; COSMIC: COSV62156457;