17-74250344-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_032646.6(TTYH2):c.1103G>A(p.Arg368Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000145 in 1,613,004 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00015 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
TTYH2
NM_032646.6 missense
NM_032646.6 missense
Scores
6
8
5
Clinical Significance
Conservation
PhyloP100: 7.27
Genes affected
TTYH2 (HGNC:13877): (tweety family member 2) 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, and may play a role in kidney tumorigenesis. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTYH2 | NM_032646.6 | c.1103G>A | p.Arg368Gln | missense_variant | 10/14 | ENST00000269346.9 | |
TTYH2 | NM_001330453.2 | c.1040G>A | p.Arg347Gln | missense_variant | 10/14 | ||
TTYH2 | NM_052869.1 | c.140G>A | p.Arg47Gln | missense_variant | 4/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTYH2 | ENST00000269346.9 | c.1103G>A | p.Arg368Gln | missense_variant | 10/14 | 1 | NM_032646.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152176Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000121 AC: 30AN: 248418Hom.: 0 AF XY: 0.000112 AC XY: 15AN XY: 134312
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GnomAD4 exome AF: 0.000144 AC: 211AN: 1460828Hom.: 0 Cov.: 32 AF XY: 0.000169 AC XY: 123AN XY: 726564
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GnomAD4 genome ? AF: 0.000151 AC: 23AN: 152176Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74332
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 15, 2023 | The c.1103G>A (p.R368Q) alteration is located in exon 10 (coding exon 10) of the TTYH2 gene. This alteration results from a G to A substitution at nucleotide position 1103, causing the arginine (R) at amino acid position 368 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Pathogenic
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D
Sift4G
Uncertain
D;D;D
Polyphen
D;D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at