rs138241615
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_004817.4(TJP2):c.185C>T(p.Thr62Met) variant causes a missense change. The variant allele was found at a frequency of 0.00239 in 1,614,136 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_004817.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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TJP2 | ENST00000377245.9 | c.185C>T | p.Thr62Met | missense_variant | Exon 3 of 23 | 1 | NM_004817.4 | ENSP00000366453.4 | ||
ENSG00000285130 | ENST00000642889.1 | c.572C>T | p.Thr191Met | missense_variant | Exon 5 of 25 | ENSP00000493780.1 |
Frequencies
GnomAD3 genomes AF: 0.00173 AC: 263AN: 152150Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00150 AC: 378AN: 251490Hom.: 2 AF XY: 0.00161 AC XY: 219AN XY: 135918
GnomAD4 exome AF: 0.00246 AC: 3592AN: 1461868Hom.: 8 Cov.: 30 AF XY: 0.00239 AC XY: 1740AN XY: 727238
GnomAD4 genome AF: 0.00172 AC: 262AN: 152268Hom.: 0 Cov.: 33 AF XY: 0.00154 AC XY: 115AN XY: 74448
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:3Other:1
TJP2: BS2 -
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GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. -
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Identified in unrelated patients with intrahepatic cholestasis of pregnancy in published literature (Dixon et al., 2017; Vitale et al., 2017); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 33390354, 31450555, 32089630, 29238877, 28924228) -
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Autosomal dominant nonsyndromic hearing loss 51 Pathogenic:1
A very rare variant predicted deleterious by most prediction programs. The type of HL is characteristic for this gene. Classified as likely pathogenic by Deafness Variation Database based on PMID: 29238877 -
Cholestasis, progressive familial intrahepatic, 4;C5542604:Hypercholanemia, familial 1 Pathogenic:1
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not specified Benign:1
Thr39Met in Exon 4 of TJP2: This variant is not expected to have clinical signi ficance because it has been observed in 0.3% (24/8600) of European American chro mosomes from a broad population by the NHLBI Exome Sequencing Project (http://ev s.gs.washington.edu/EVS; dbSNP rs138241615). -
TJP2-related disorder Benign:1
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at