chr2-256278-T-C

Variant names:

• chr2-256278-T-C
• rs4455191
• ENST00000626873.2:c.-493A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001282687.2(SH3YL1):​c.-493A>G variant causes a 5 prime UTR 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_001282687.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.423
• Publications: 15 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001282687.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3YL1	NM_015677.4	MANE Select	c.2-3163A>G		intron	N/A	NP_056492.2	Q96HL8-1
	SH3YL1	NM_001282687.2		c.-493A>G		5_prime_UTR	Exon 1 of 12	NP_001269616.1	Q96HL8-3
	SH3YL1	NM_001159597.3		c.2-3163A>G		intron	N/A	NP_001153069.1	Q96HL8-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3YL1	ENST00000626873.2	TSL:5	c.-493A>G		5_prime_UTR	Exon 2 of 13	ENSP00000485824.1	Q96HL8-3
	SH3YL1	ENST00000356150.10	TSL:1 MANE Select	c.2-3163A>G		intron	N/A	ENSP00000348471.5	Q96HL8-1
	SH3YL1	ENST00000403712.6	TSL:1	c.2-3163A>G		intron	N/A	ENSP00000384276.1	Q96HL8-2

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 4 AN: 8

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.0980 AC: 4072 AN: 41564

American (AMR) AF: 0.262 AC: 4010 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.326 AC: 1131 AN: 3470

East Asian (EAS) AF: 0.527 AC: 2734 AN: 5184

South Asian (SAS) AF: 0.258 AC: 1249 AN: 4832

European-Finnish (FIN) AF: 0.398 AC: 4209 AN: 10588

Middle Eastern (MID) AF: 0.337 AC: 99 AN: 294

European-Non Finnish (NFE) AF: 0.344 AC: 23389 AN: 67992

Other (OTH) AF: 0.279 AC: 588 AN: 2108

Alfa AF: 0.302 Hom.: 5615

Bravo AF: 0.258

Asia WGS AF: 0.319 AC: 1108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.48
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4455191; hg19: chr2-256278;