Variant 7-2632175-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000258796.12(TTYH3):c.20C>G(p.Ala7Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000745 in 1,342,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

TTYH3
ENST00000258796.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.887

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12489766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTYH3	NM_025250.3 linkuse as main transcript	c.20C>G	p.Ala7Gly	missense_variant	1/14	ENST00000258796.12	NP_079526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTYH3	ENST00000258796.12 linkuse as main transcript	c.20C>G	p.Ala7Gly	missense_variant	1/14	1	NM_025250.3	ENSP00000258796	P3	Q9C0H2-1
TTYH3	ENST00000429448.2 linkuse as main transcript	c.20C>G	p.Ala7Gly	missense_variant	1/15	2		ENSP00000413757	A1	Q9C0H2-4
TTYH3	ENST00000407643.5 linkuse as main transcript	c.20C>G	p.Ala7Gly	missense_variant	1/13	5		ENSP00000385316		Q9C0H2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000804

AC:

AN:

124380

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

68090

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000146

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.45e-7

AC:

AN:

1342850

Hom.:

Cov.:

AF XY:

0.00000151

AC XY:

AN XY:

662974

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000315

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 21, 2022

The c.20C>G (p.A7G) alteration is located in exon 1 (coding exon 1) of the TTYH3 gene. This alteration results from a C to G substitution at nucleotide position 20, causing the alanine (A) at amino acid position 7 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

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

T;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.46

LIST_S2

Uncertain

0.92

D;D

M_CAP

Uncertain

0.26

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;N

MutationTaster

Benign

0.77

N;N

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.054

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.031

D;T

Polyphen

0.30

B;.

Vest4

0.066

MutPred

0.28

Gain of disorder (P = 0.0889);Gain of disorder (P = 0.0889);

MVP

0.043

MPC

0.31

ClinPred

0.11

GERP RS

3.9

Varity_R

0.23

gMVP

0.30

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