11-121152938-G-A
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS1
The NM_005422.4(TECTA):c.4163G>A(p.Arg1388His) variant causes a missense change. The variant allele was found at a frequency of 0.000208 in 1,612,800 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1388C) has been classified as Uncertain significance.
Frequency
Consequence
NM_005422.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TECTA | NM_005422.4 | c.4163G>A | p.Arg1388His | missense_variant | 13/24 | ENST00000392793.6 | |
TBCEL-TECTA | NM_001378761.1 | c.5120G>A | p.Arg1707His | missense_variant | 19/30 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TECTA | ENST00000392793.6 | c.4163G>A | p.Arg1388His | missense_variant | 13/24 | 5 | NM_005422.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152166Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000367 AC: 92AN: 250892Hom.: 1 AF XY: 0.000501 AC XY: 68AN XY: 135664
GnomAD4 exome AF: 0.000212 AC: 309AN: 1460516Hom.: 1 Cov.: 31 AF XY: 0.000275 AC XY: 200AN XY: 726248
GnomAD4 genome AF: 0.000171 AC: 26AN: 152284Hom.: 0 Cov.: 33 AF XY: 0.000242 AC XY: 18AN XY: 74464
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2023 | - - |
Autosomal recessive nonsyndromic hearing loss 21 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
Autosomal dominant nonsyndromic hearing loss 12 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 12, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at