2-242800-T-C

Variant names:

• chr2-242800-T-C
• rs10181051
• ENST00000626873.2:c.1A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000626873.2(SH3YL1):​c.1A>G​(p.Met1?) variant causes a start lost, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.382 in 1,532,826 control chromosomes in the GnomAD database, including 115,767 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.34 (9302 hom., cov: 32)
  • Exomes 𝑓: 0.39 (106465 hom.)
• Consequence: SH3YL1 ENST00000626873.2 start_lost, splice_region
• Scores: Splicing: ADA: 0.00006740
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.207
• Publications: 16 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.574 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000626873.2. 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+4738A>G		intron	N/A	NP_056492.2
	SH3YL1	NM_001282687.2		c.1A>G	p.Met1?	start_lost splice_region	Exon 6 of 12	NP_001269616.1
	SH3YL1	NM_001282682.2		c.1A>G	p.Met1?	start_lost splice_region	Exon 6 of 11	NP_001269611.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3YL1	ENST00000626873.2	TSL:5	c.1A>G	p.Met1?	start_lost splice_region	Exon 7 of 13	ENSP00000485824.1
	SH3YL1	ENST00000356150.10	TSL:1 MANE Select	c.291+4738A>G		intron	N/A	ENSP00000348471.5
	SH3YL1	ENST00000403712.6	TSL:1	c.291+4738A>G		intron	N/A	ENSP00000384276.1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50927 AN: 151858 Hom.: 9308 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.270

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.379

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.333

GnomAD2 exomes AF: 0.351 AC: 48348 AN: 137938 AF XY: 0.351

Gnomad AFR exome AF: 0.180

Gnomad AMR exome AF: 0.248

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.586

Gnomad FIN exome AF: 0.424

Gnomad NFE exome AF: 0.386

Gnomad OTH exome AF: 0.337

GnomAD4 exome AF: 0.387 AC: 534155 AN: 1380852 Hom.: 106465 Cov.: 35 AF XY: 0.384 AC XY: 261779 AN XY: 681068

African (AFR) AF: 0.190 AC: 5880 AN: 30922

American (AMR) AF: 0.259 AC: 8489 AN: 32752

Ashkenazi Jewish (ASJ) AF: 0.342 AC: 8474 AN: 24742

East Asian (EAS) AF: 0.597 AC: 20433 AN: 34246

South Asian (SAS) AF: 0.278 AC: 21153 AN: 76118

European-Finnish (FIN) AF: 0.428 AC: 20703 AN: 48390

Middle Eastern (MID) AF: 0.327 AC: 1842 AN: 5640

European-Non Finnish (NFE) AF: 0.397 AC: 425632 AN: 1070838

Other (OTH) AF: 0.377 AC: 21549 AN: 57204

GnomAD4 genome AF: 0.335 AC: 50929 AN: 151974 Hom.: 9302 Cov.: 32 AF XY: 0.338 AC XY: 25123 AN XY: 74272

African (AFR) AF: 0.198 AC: 8194 AN: 41460

American (AMR) AF: 0.305 AC: 4655 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 1174 AN: 3468

East Asian (EAS) AF: 0.591 AC: 3059 AN: 5174

South Asian (SAS) AF: 0.281 AC: 1352 AN: 4818

European-Finnish (FIN) AF: 0.445 AC: 4687 AN: 10540

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.394 AC: 26751 AN: 67922

Other (OTH) AF: 0.333 AC: 702 AN: 2106

Alfa AF: 0.365 Hom.: 20328

Bravo AF: 0.321

TwinsUK AF: 0.392 AC: 1455

ALSPAC AF: 0.399 AC: 1536

ESP6500AA AF: 0.194 AC: 421

ESP6500EA AF: 0.386 AC: 1675

ExAC AF: 0.307 AC: 7156

Asia WGS AF: 0.375 AC: 1301 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	12
DANN	Benign	0.51
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.87
FATHMM_MKL	Benign	0.012	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.000070	T
MetaSVM	Benign	-0.98	T
PhyloP100		0.21
PROVEAN	Benign	0.030	N
REVEL	Benign	0.013
Sift	Pathogenic	0.0	D
Polyphen		0.011	B
Vest4		0.18
ClinPred		0.025	T
GERP RS		0.13
Mutation Taster		=102/98	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000067
dbscSNV1_RF	Benign	0.0060
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: rs10181051; hg19: chr2-242800; COSMIC: COSV62158234;