chr2-233200-C-T

Variant names:

• chr2-233200-C-T
• rs902274112
• NM_015677.4:c.434G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015677.4(SH3YL1):​c.434G>A​(p.Ser145Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000349 in 1,432,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SH3YL1 NM_015677.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.16
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35481325).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3YL1	NM_015677.4	MANE Select	c.434G>A	p.Ser145Asn	missense	Exon 6 of 10	NP_056492.2	Q96HL8-1
	SH3YL1	NM_001159597.3		c.434G>A	p.Ser145Asn	missense	Exon 6 of 9	NP_001153069.1	Q96HL8-2
	SH3YL1	NM_001282687.2		c.146G>A	p.Ser49Asn	missense	Exon 8 of 12	NP_001269616.1	Q96HL8-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SH3YL1	ENST00000356150.10	TSL:1 MANE Select	c.434G>A	p.Ser145Asn	missense	Exon 6 of 10	ENSP00000348471.5	Q96HL8-1
	SH3YL1	ENST00000403712.6	TSL:1	c.434G>A	p.Ser145Asn	missense	Exon 6 of 9	ENSP00000384276.1	Q96HL8-2
	SH3YL1	ENST00000626873.2	TSL:5	c.146G>A	p.Ser49Asn	missense	Exon 9 of 13	ENSP00000485824.1	Q96HL8-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000421 AC: 1 AN: 237446 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000349 AC: 5 AN: 1432872 Hom.: 0 Cov.: 30 AF XY: 0.00000421 AC XY: 3 AN XY: 712552

African (AFR) AF: 0.00 AC: 0 AN: 32730

American (AMR) AF: 0.00 AC: 0 AN: 41078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25386

East Asian (EAS) AF: 0.00 AC: 0 AN: 38964

South Asian (SAS) AF: 0.0000122 AC: 1 AN: 82112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52438

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5650

European-Non Finnish (NFE) AF: 0.00000274 AC: 3 AN: 1095756

Other (OTH) AF: 0.0000170 AC: 1 AN: 58758

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	T
Eigen	Benign	0.0095
Eigen_PC	Benign	-0.066
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.061	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		5.2
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.23
Sift	Benign	0.12	T
Sift4G	Benign	0.067	T
Polyphen		0.97	D
Vest4		0.55
MutPred		0.63		Gain of helix (P = 0.0696)
MVP		0.25
MPC		0.34
ClinPred		0.49	T
GERP RS		4.8
Varity_R		0.13
gMVP		0.69
Mutation Taster		=75/25	polymorphism

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: rs902274112; hg19: chr2-233200;