Genetic Variant SH3TC1:p.Arg118Leu (chr4-8212806-G-T) – 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_018986.5(SH3TC1):c.353G>T(p.Arg118Leu) variant causes a missense 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R118Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SH3TC1
NM_018986.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.252

Publications

4 publications found

Variant links:

Genes affected

SH3TC1 (HGNC:26009): (SH3 domain and tetratricopeptide repeats 1)

SH3TC1 links:

Genome browser will be placed here

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=0.118745714).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018986.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3TC1	NM_018986.5	MANE Select	c.353G>T	p.Arg118Leu	missense	Exon 4 of 18	NP_061859.4
SH3TC1	NM_001410712.1		c.353G>T	p.Arg118Leu	missense	Exon 4 of 18	NP_001397641.1	A0A804HI81
SH3TC1	NM_001318480.2		c.125G>T	p.Arg42Leu	missense	Exon 4 of 18	NP_001305409.2	H0YA34

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SH3TC1	ENST00000245105.8	TSL:2 MANE Select	c.353G>T	p.Arg118Leu	missense	Exon 4 of 18	ENSP00000245105.3	Q8TE82
SH3TC1	ENST00000502669.5	TSL:1	n.278G>T		non_coding_transcript_exon	Exon 3 of 15	ENSP00000425970.1	D6RI07
SH3TC1	ENST00000457650.7	TSL:5	c.353G>T	p.Arg118Leu	missense	Exon 5 of 19	ENSP00000390311.3	Q8TE82

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1446972

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718338

African (AFR)

AF:

0.00

AC:

AN:

33288

American (AMR)

AF:

0.00

AC:

AN:

42832

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25678

East Asian (EAS)

AF:

0.00

AC:

AN:

39152

South Asian (SAS)

AF:

0.00

AC:

AN:

83874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5384

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1105214

Other (OTH)

AF:

0.00

AC:

AN:

59734

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.017

BayesDel_noAF

Benign

-0.26

CADD

Benign

9.4

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.023

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.63

M_CAP

Benign

0.029

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.69

MutationAssessor

Benign

1.8

PhyloP100

0.25

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.16

Sift

Benign

0.051

Sift4G

Uncertain

0.052

Polyphen

0.018

Vest4

0.28

MutPred

0.34

Gain of glycosylation at S117 (P = 0.0103)

MVP

0.70

MPC

0.034

ClinPred

0.12

GERP RS

2.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.088

gMVP

0.24

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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