7-2647478-C-A

Variant names:

• chr7-2647478-C-A
• rs200994245
• NM_025250.3:c.466C>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_025250.3(TTYH3):​c.466C>A​(p.Arg156Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,382,972 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: 7.2e-7 (0 hom.)
• Consequence: TTYH3 NM_025250.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.676
• 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BP7: Synonymous conserved (PhyloP=0.676 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.466C>A	p.Arg156Arg	synonymous	Exon 4 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.466C>A	p.Arg156Arg	synonymous	Exon 4 of 14	ENSP00000258796.7	Q9C0H2-1
	TTYH3	ENST00000913086.1		c.775C>A	p.Arg259Arg	synonymous	Exon 5 of 15	ENSP00000583145.1
	TTYH3	ENST00000913085.1		c.466C>A	p.Arg156Arg	synonymous	Exon 4 of 15	ENSP00000583144.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1382972 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 681858

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 31416

American (AMR) AF: 0.00 AC: 0 AN: 35552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25068

East Asian (EAS) AF: 0.00 AC: 0 AN: 35606

South Asian (SAS) AF: 0.00 AC: 0 AN: 79008

European-Finnish (FIN) AF: 0.0000261 AC: 1 AN: 38308

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1076336

Other (OTH) AF: 0.00 AC: 0 AN: 57542

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	10
DANN	Benign	0.43
PhyloP100		0.68
PromoterAI		0.012	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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: rs200994245; hg19: chr7-2687112;