7-2632175-C-T

Variant names:

• chr7-2632175-C-T
• rs1342658130
• NM_025250.3:c.20C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025250.3(TTYH3):​c.20C>T​(p.Ala7Val) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.4e-7 (0 hom.)
• Consequence: TTYH3 NM_025250.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.887

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]

ACMG classification

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=0.119041204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTYH3	NM_025250.3	c.20C>T	p.Ala7Val	missense_variant	Exon 1 of 14	ENST00000258796.12	NP_079526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTYH3	ENST00000258796.12	c.20C>T	p.Ala7Val	missense_variant	Exon 1 of 14	1	NM_025250.3	ENSP00000258796.7
TTYH3	ENST00000429448.2	c.20C>T	p.Ala7Val	missense_variant	Exon 1 of 15	2		ENSP00000413757.2
TTYH3	ENST00000407643.5	c.20C>T	p.Ala7Val	missense_variant	Exon 1 of 13	5		ENSP00000385316.1

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 7.45e-7 AC: 1 AN: 1342850 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 662974

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000183

GnomAD4 genome Cov.: 30

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	21
DANN	Benign	0.73
DEOGEN2	Benign	0.063	T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.25
FATHMM_MKL	Benign	0.45	N
LIST_S2	Uncertain	0.90	D;D
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-0.34	N;N
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.18	N;N
REVEL	Benign	0.078
Sift	Benign	1.0	T;T
Sift4G	Uncertain	0.027	D;T
Polyphen		0.49	P;.
Vest4		0.091
MutPred		0.32		Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);
MVP		0.043
MPC		0.28
ClinPred		0.58	D
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.086
gMVP		0.33

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

Other links and lift over

dbSNP: rs1342658130; hg19: chr7-2671809;