rs150889231

Variant names:

• chr7-2646930-G-A
• NM_025250.3:c.201G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-2646930-G-A
• chr7-2646930-G-T

Variant summary

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

The NM_025250.3(TTYH3):​c.201G>A​(p.Trp67*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,449,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TTYH3 NM_025250.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.11

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TTYH3	NM_025250.3	c.201G>A	p.Trp67*	stop_gained	Exon 2 of 14	ENST00000258796.12	NP_079526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TTYH3	ENST00000258796.12	c.201G>A	p.Trp67*	stop_gained	Exon 2 of 14	1	NM_025250.3	ENSP00000258796.7
TTYH3	ENST00000429448.2	c.201G>A	p.Trp67*	stop_gained	Exon 2 of 15	2		ENSP00000413757.2
TTYH3	ENST00000407643.5	c.201G>A	p.Trp67*	stop_gained	Exon 2 of 13	5		ENSP00000385316.1
TTYH3	ENST00000400376.2	c.222G>A	p.Trp74*	stop_gained	Exon 2 of 3	4		ENSP00000383227.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1449078 Hom.: 0 Cov.: 46 AF XY: 0.00000139 AC XY: 1 AN XY: 721256

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.48	D
BayesDel_noAF	Pathogenic	0.45
CADD	Pathogenic	44
DANN	Uncertain	1.0
Eigen	Pathogenic	0.94
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.97	D
Vest4		0.32
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-2686564;