7-2649984-T-A

Position:

• chr7-2649984-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000258796.12(TTYH3):​c.867T>A​(p.Ser289Arg) variant causes a missense 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TTYH3 ENST00000258796.12 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.244

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18663228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TTYH3	NM_025250.3	c.867T>A	p.Ser289Arg	missense_variant	7/14	ENST00000258796.12	NP_079526.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TTYH3	ENST00000258796.12	c.867T>A	p.Ser289Arg	missense_variant	7/14	1	NM_025250.3	ENSP00000258796	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 26, 2022

The c.867T>A (p.S289R) alteration is located in exon 7 (coding exon 7) of the TTYH3 gene. This alteration results from a T to A substitution at nucleotide position 867, causing the serine (S) at amino acid position 289 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.42
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L;.;.
MutationTaster	Benign	0.73	N;N;N
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.0	D;D;D
REVEL	Benign	0.063
Sift	Benign	0.072	T;T;T
Sift4G	Benign	0.16	T;T;T
Polyphen		0.0010	B;.;B
Vest4		0.33
MutPred		0.60		Loss of helix (P = 0.028);.;.;
MVP		0.043
MPC		0.25
ClinPred		0.53	D
GERP RS		-1.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.22
gMVP		0.43

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-2689618;