chr11-18701924-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_153347.3(TMEM86A):āc.638A>Gā(p.Tyr213Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,628 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_153347.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMEM86A | NM_153347.3 | c.638A>G | p.Tyr213Cys | missense_variant | 3/3 | ENST00000280734.3 | NP_699178.1 | |
TMEM86A | XM_047426448.1 | c.638A>G | p.Tyr213Cys | missense_variant | 3/4 | XP_047282404.1 | ||
TMEM86A | XM_047426449.1 | c.638A>G | p.Tyr213Cys | missense_variant | 3/5 | XP_047282405.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM86A | ENST00000280734.3 | c.638A>G | p.Tyr213Cys | missense_variant | 3/3 | 1 | NM_153347.3 | ENSP00000280734 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251286Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135842
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461628Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727134
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2021 | The c.638A>G (p.Y213C) alteration is located in exon 3 (coding exon 3) of the TMEM86A gene. This alteration results from a A to G substitution at nucleotide position 638, causing the tyrosine (Y) at amino acid position 213 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at