rs41348347
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000361.3(THBD):c.1456G>T(p.Asp486Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00202 in 1,612,354 control chromosomes in the GnomAD database, including 79 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. D486D) has been classified as Likely benign.
Frequency
Consequence
NM_000361.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
THBD | NM_000361.3 | c.1456G>T | p.Asp486Tyr | missense_variant | 1/1 | ENST00000377103.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
THBD | ENST00000377103.3 | c.1456G>T | p.Asp486Tyr | missense_variant | 1/1 | NM_000361.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00287 AC: 437AN: 152260Hom.: 10 Cov.: 33
GnomAD3 exomes AF: 0.00838 AC: 2054AN: 245174Hom.: 58 AF XY: 0.00646 AC XY: 861AN XY: 133248
GnomAD4 exome AF: 0.00193 AC: 2820AN: 1459976Hom.: 69 Cov.: 30 AF XY: 0.00174 AC XY: 1261AN XY: 726292
GnomAD4 genome ? AF: 0.00288 AC: 439AN: 152378Hom.: 10 Cov.: 33 AF XY: 0.00297 AC XY: 221AN XY: 74512
ClinVar
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 27, 2020 | This variant is associated with the following publications: (PMID: 26034596, 7811989, 19625716, 25135378, 20595690, 23332921) - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Thrombomodulin-related bleeding disorder Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Aug 01, 2002 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Oct 24, 2019 | - - |
THBD-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 05, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Kidney disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome Diagnostics Laboratory, The Hospital for Sick Children | Mar 01, 2020 | - - |
Atypical hemolytic-uremic syndrome with thrombomodulin anomaly Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at