NM_015677.4:c.589C>A

Variant names:

• chr2-231136-G-T
• rs1439675896
• NM_015677.4:c.589C>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_015677.4(SH3YL1):​c.589C>A​(p.Pro197Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SH3YL1 NM_015677.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.06
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.799

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.589C>A	p.Pro197Thr	missense	Exon 7 of 10	NP_056492.2	Q96HL8-1
	SH3YL1	NM_001159597.3		c.589C>A	p.Pro197Thr	missense	Exon 7 of 9	NP_001153069.1	Q96HL8-2
	SH3YL1	NM_001282687.2		c.301C>A	p.Pro101Thr	missense	Exon 9 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.589C>A	p.Pro197Thr	missense	Exon 7 of 10	ENSP00000348471.5	Q96HL8-1
	SH3YL1	ENST00000403712.6	TSL:1	c.589C>A	p.Pro197Thr	missense	Exon 7 of 9	ENSP00000384276.1	Q96HL8-2
	SH3YL1	ENST00000626873.2	TSL:5	c.301C>A	p.Pro101Thr	missense	Exon 10 of 13	ENSP00000485824.1	Q96HL8-3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.27
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.060
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D
Eigen	Uncertain	0.64
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.044	D
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.55	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		8.1
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-7.2	D
REVEL	Uncertain	0.39
Sift	Uncertain	0.0020	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.72
MutPred		0.57		Gain of phosphorylation at P197 (P = 0.0489)
MVP		0.55
MPC		0.47
ClinPred		1.0	D
GERP RS		4.2
Varity_R		0.69
gMVP		0.80
Mutation Taster		=65/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1439675896; hg19: chr2-231136;