Genetic Variant SH3YL1:p.Ala235Pro (chr2-230044-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_015677.4(SH3YL1):c.703G>C(p.Ala235Pro) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SH3YL1
NM_015677.4 missense, splice_region

Scores

Splicing: ADA: 0.4700

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.05

Publications

2 publications found

Variant links:

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]

SH3YL1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16330743).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3YL1	NM_015677.4	MANE Select	c.703G>C	p.Ala235Pro	missense splice_region	Exon 8 of 10	NP_056492.2	Q96HL8-1
SH3YL1	NM_001159597.3		c.703G>C	p.Ala235Pro	missense splice_region	Exon 8 of 9	NP_001153069.1	Q96HL8-2
SH3YL1	NM_001282687.2		c.415G>C	p.Ala139Pro	missense splice_region	Exon 10 of 12	NP_001269616.1	Q96HL8-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3YL1	ENST00000356150.10	TSL:1 MANE Select	c.703G>C	p.Ala235Pro	missense splice_region	Exon 8 of 10	ENSP00000348471.5	Q96HL8-1
SH3YL1	ENST00000403712.6	TSL:1	c.703G>C	p.Ala235Pro	missense splice_region	Exon 8 of 9	ENSP00000384276.1	Q96HL8-2
SH3YL1	ENST00000626873.2	TSL:5	c.415G>C	p.Ala139Pro	missense splice_region	Exon 11 of 13	ENSP00000485824.1	Q96HL8-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1441872

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

716028

African (AFR)

AF:

0.00

AC:

AN:

32670

American (AMR)

AF:

0.00

AC:

AN:

41950

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25452

East Asian (EAS)

AF:

0.00

AC:

AN:

39408

South Asian (SAS)

AF:

0.00

AC:

AN:

82706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53040

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5662

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1101470

Other (OTH)

AF:

0.00

AC:

AN:

59514

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.73

M_CAP

Benign

0.013

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

1.0

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.55

REVEL

Benign

0.076

Sift

Benign

0.14

Sift4G

Benign

0.29

Polyphen

0.0010

Vest4

0.17

MutPred

0.33

Gain of glycosylation at A235 (P = 0.0087)

MVP

0.40

MPC

0.10

ClinPred

0.17

GERP RS

4.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.59

Mutation Taster

=60/40

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.47

dbscSNV1_RF

Benign

0.49

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over