Variant 7-2647478-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025250.3(TTYH3):c.466C>G(p.Arg156Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000155 in 1,535,270 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000089 ( 1 hom. )

Consequence

TTYH3
NM_025250.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.676

Variant links:

Genes affected

TTYH3 (HGNC:22222): (tweety family member 3) This gene encodes a member of the tweety family of proteins. Members of this family function as chloride anion channels. The encoded protein functions as a calcium(2+)-activated large conductance chloride(-) channel. [provided by RefSeq, Jul 2008]

TTYH3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008799404).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTYH3	NM_025250.3 linkuse as main transcript	c.466C>G	p.Arg156Gly	missense_variant	4/14	ENST00000258796.12	NP_079526.1	Q9C0H2-1A0A024R816Q8WYU9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TTYH3	ENST00000258796.12 linkuse as main transcript	c.466C>G	p.Arg156Gly	missense_variant	4/14	1	NM_025250.3	ENSP00000258796.7	Q9C0H2-1
TTYH3	ENST00000429448.2 linkuse as main transcript	c.466C>G	p.Arg156Gly	missense_variant	4/15	2		ENSP00000413757.2	Q9C0H2-4H7C3T6
TTYH3	ENST00000407643.5 linkuse as main transcript	c.466C>G	p.Arg156Gly	missense_variant	4/13	5		ENSP00000385316.1	Q9C0H2-2

Frequencies

GnomAD3 genomes

AF:

0.000756

AC:

115

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00251

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000154

AC:

AN:

136716

Hom.:

AF XY:

0.000134

AC XY:

AN XY:

74438

show subpopulations

Gnomad AFR exome

AF:

0.00268

Gnomad AMR exome

AF:

0.0000818

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000191

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000889

AC:

123

AN:

1382972

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

681858

show subpopulations

Gnomad4 AFR exome

AF:

0.00344

Gnomad4 AMR exome

AF:

0.0000844

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000253

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000186

Gnomad4 OTH exome

AF:

0.000139

GnomAD4 genome

AF:

0.000755

AC:

115

AN:

152298

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00250

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000820

ExAC

AF:

0.000112

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

Apr 25, 2022

The c.466C>G (p.R156G) alteration is located in exon 4 (coding exon 4) of the TTYH3 gene. This alteration results from a C to G substitution at nucleotide position 466, causing the arginine (R) at amino acid position 156 to be replaced by a glycine (G). 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

0.072

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.31

T;.

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.0088

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.14

N;N

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.044

Sift

Uncertain

0.023

D;D

Sift4G

Benign

0.23

T;T

Polyphen

0.0

B;.

Vest4

0.12

MVP

0.043

MPC

0.29

ClinPred

0.018

GERP RS

3.4

Varity_R

0.13

gMVP

0.38

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