7-2646942-G-C

Variant names:

• chr7-2646942-G-C
• NM_025250.3:c.213G>C
• TTYH3 p.Arg71Arg

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_025250.3(TTYH3):​c.213G>C​(p.Arg71Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 33)
• Consequence: TTYH3 NM_025250.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.360
• 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: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.64).
• BP7: Synonymous conserved (PhyloP=0.36 with no splicing effect.

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.213G>C	p.Arg71Arg	synonymous	Exon 2 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.213G>C	p.Arg71Arg	synonymous	Exon 2 of 14	ENSP00000258796.7	Q9C0H2-1
	TTYH3	ENST00000913086.1		c.522G>C	p.Arg174Arg	synonymous	Exon 3 of 15	ENSP00000583145.1
	TTYH3	ENST00000913085.1		c.213G>C	p.Arg71Arg	synonymous	Exon 2 of 15	ENSP00000583144.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.64
CADD	Benign	7.6
DANN	Benign	0.63
PhyloP100		0.36

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-2686576;