7-2647197-A-C

Variant names:

• chr7-2647197-A-C
• rs372276388
• NM_025250.3:c.349A>C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_025250.3(TTYH3):​c.349A>C​(p.Arg117Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,454,312 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: TTYH3 NM_025250.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.24

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP7: Synonymous conserved (PhyloP=2.24 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTYH3	NM_025250.3	c.349A>C	p.Arg117Arg	synonymous_variant	Exon 3 of 14	ENST00000258796.12	NP_079526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTYH3	ENST00000258796.12	c.349A>C	p.Arg117Arg	synonymous_variant	Exon 3 of 14	1	NM_025250.3	ENSP00000258796.7
TTYH3	ENST00000429448.2	c.349A>C	p.Arg117Arg	synonymous_variant	Exon 3 of 15	2		ENSP00000413757.2
TTYH3	ENST00000407643.5	c.349A>C	p.Arg117Arg	synonymous_variant	Exon 3 of 13	5		ENSP00000385316.1
TTYH3	ENST00000400376.2	c.*21A>C		downstream_gene_variant		4		ENSP00000383227.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000158 AC: 23 AN: 1454312 Hom.: 0 Cov.: 33 AF XY: 0.00000692 AC XY: 5 AN XY: 723050

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: 0.0000207

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.78
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs372276388; hg19: chr7-2686831;