Variant 7-2646940-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025250.3(TTYH3):c.211C>G(p.Arg71Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000345 in 1,448,630 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000035 ( 0 hom. )

Consequence

TTYH3
NM_025250.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.76

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTYH3	NM_025250.3 linkuse as main transcript	c.211C>G	p.Arg71Gly	missense_variant	2/14	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.211C>G	p.Arg71Gly	missense_variant	2/14	1	NM_025250.3	ENSP00000258796.7	Q9C0H2-1
TTYH3	ENST00000429448.2 linkuse as main transcript	c.211C>G	p.Arg71Gly	missense_variant	2/15	2		ENSP00000413757.2	Q9C0H2-4H7C3T6
TTYH3	ENST00000407643.5 linkuse as main transcript	c.211C>G	p.Arg71Gly	missense_variant	2/13	5		ENSP00000385316.1	Q9C0H2-2
TTYH3	ENST00000400376.2 linkuse as main transcript	c.232C>G	p.Arg78Gly	missense_variant	2/3	4		ENSP00000383227.2	A8MXJ9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000129

AC:

AN:

231786

Hom.:

AF XY:

0.00000788

AC XY:

AN XY:

126956

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000590

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000337

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000345

AC:

AN:

1448630

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

720876

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000450

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000166

AC:

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

Sep 27, 2022

The c.211C>G (p.R71G) alteration is located in exon 2 (coding exon 2) of the TTYH3 gene. This alteration results from a C to G substitution at nucleotide position 211, causing the arginine (R) at amino acid position 71 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

0.19

BayesDel_addAF

Uncertain

0.039

BayesDel_noAF

Uncertain

0.0

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

T;.;.

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

D;D;D

M_CAP

Benign

0.084

MetaRNN

Uncertain

0.55

D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M;.

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.7

D;D;D

REVEL

Benign

0.28

Sift

Benign

0.29

T;T;T

Sift4G

Uncertain

0.059

T;T;D

Polyphen

1.0

D;.;.

Vest4

0.85

MutPred

0.53

Gain of ubiquitination at K74 (P = 0.0662);Gain of ubiquitination at K74 (P = 0.0662);.;

MVP

0.21

MPC

0.43

ClinPred

0.71

GERP RS

5.0

Varity_R

0.56

gMVP

0.69

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