Variant 4-8212818-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_018986.5(SH3TC1):c.365G>A(p.Arg122His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000998 in 1,583,890 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00062 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0010 ( 4 hom. )

Consequence

SH3TC1
NM_018986.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.275

Variant links:

Genes affected

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

SH3TC1 links:

SH3TC1 (HGNC:):

SH3TC1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011543393).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3TC1	NM_018986.5 linkuse as main transcript	c.365G>A	p.Arg122His	missense_variant	4/18	ENST00000245105.8	NP_061859.4	Q8TE82B3KWX8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3TC1	ENST00000245105.8 linkuse as main transcript	c.365G>A	p.Arg122His	missense_variant	4/18	2	NM_018986.5	ENSP00000245105.3		Q8TE82

Frequencies

GnomAD3 genomes

AF:

0.000618

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00119

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000514

AC:

101

AN:

196640

Hom.:

AF XY:

0.000546

AC XY:

AN XY:

106216

show subpopulations

Gnomad AFR exome

AF:

0.000257

Gnomad AMR exome

AF:

0.000172

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000132

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00101

Gnomad OTH exome

AF:

0.000198

GnomAD4 exome

AF:

0.00104

AC:

1486

AN:

1431558

Hom.:

Cov.:

AF XY:

0.00103

AC XY:

731

AN XY:

709432

show subpopulations

Gnomad4 AFR exome

AF:

0.000212

Gnomad4 AMR exome

AF:

0.000296

Gnomad4 ASJ exome

AF:

0.0000396

Gnomad4 EAS exome

AF:

0.000104

Gnomad4 SAS exome

AF:

0.000146

Gnomad4 FIN exome

AF:

0.0000197

Gnomad4 NFE exome

AF:

0.00128

Gnomad4 OTH exome

AF:

0.000778

GnomAD4 genome

AF:

0.000617

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000618

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00119

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000857

Hom.:

Bravo

AF:

0.000688

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000229

AC:

ESP6500EA

AF:

0.000817

AC:

ExAC

AF:

0.000416

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 12, 2023

The c.365G>A (p.R122H) alteration is located in exon 4 (coding exon 3) of the SH3TC1 gene. This alteration results from a G to A substitution at nucleotide position 365, causing the arginine (R) at amino acid position 122 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0022

.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

.;L

PrimateAI

Benign

0.45

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.072

Sift

Benign

0.25

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.052

.;B

Vest4

0.21

MVP

0.47

MPC

0.032

ClinPred

0.0060

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.042

gMVP

0.18

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over