17-80201793-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBS1_SupportingBS2_Supporting
The NM_001366385.1(CARD14):c.1901C>T(p.Thr634Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T634T) has been classified as Likely benign.
Frequency
Consequence
NM_001366385.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CARD14 | NM_001366385.1 | c.1901C>T | p.Thr634Met | missense_variant | 17/24 | ENST00000648509.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CARD14 | ENST00000648509.2 | c.1901C>T | p.Thr634Met | missense_variant | 17/24 | NM_001366385.1 | P1 | ||
ENST00000570309.1 | n.3279G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes AF: 0.000177 AC: 27AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251282Hom.: 0 AF XY: 0.0000294 AC XY: 4AN XY: 135838
GnomAD4 exome AF: 0.0000274 AC: 40AN: 1461554Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 727090
GnomAD4 genome AF: 0.000177 AC: 27AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.000215 AC XY: 16AN XY: 74444
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 13, 2021 | The c.1901C>T (p.T634M) alteration is located in exon 14 (coding exon 13) of the CARD14 gene. This alteration results from a C to T substitution at nucleotide position 1901, causing the threonine (T) at amino acid position 634 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Pityriasis rubra pilaris;C1864497:Psoriasis 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 634 of the CARD14 protein (p.Thr634Met). This variant is present in population databases (rs141847758, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with CARD14-related conditions. ClinVar contains an entry for this variant (Variation ID: 583194). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CARD14 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at