7-2632175-C-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A7G) has been classified as Uncertain significance.

• 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.119041204).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025250.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTYH3	NM_025250.3	MANE Select	c.20C>T	p.Ala7Val	missense	Exon 1 of 14	NP_079526.1	Q9C0H2-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TTYH3	ENST00000258796.12	TSL:1 MANE Select	c.20C>T	p.Ala7Val	missense	Exon 1 of 14	ENSP00000258796.7	Q9C0H2-1
	TTYH3	ENST00000913086.1		c.20C>T	p.Ala7Val	missense	Exon 1 of 15	ENSP00000583145.1
	TTYH3	ENST00000913085.1		c.20C>T	p.Ala7Val	missense	Exon 1 of 15	ENSP00000583144.1

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

African (AFR) AF: 0.00 AC: 0 AN: 28716

American (AMR) AF: 0.00 AC: 0 AN: 32582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23534

East Asian (EAS) AF: 0.00 AC: 0 AN: 31782

South Asian (SAS) AF: 0.00 AC: 0 AN: 73926

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 46230

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5168

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1046214

Other (OTH) AF: 0.0000183 AC: 1 AN: 54698

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.89
PrimateAI	Pathogenic	0.84	D
PROVEAN	Benign	0.18	N
REVEL	Benign	0.078
Sift	Benign	1.0	T
Sift4G	Uncertain	0.027	D
Polyphen		0.49	P
Vest4		0.091
MutPred		0.32		Loss of loop (P = 0.0804)
MVP		0.043
MPC		0.28
ClinPred		0.58	D
GERP RS		3.9
PromoterAI		0.035	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.086
gMVP		0.33
Mutation Taster		=77/23	polymorphism

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

Other links and lift over

dbSNP: rs1342658130; hg19: chr7-2671809;