11-18701804-G-A
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_153347.3(TMEM86A):c.518G>A(p.Arg173His) variant causes a missense change. The variant allele was found at a frequency of 0.0000496 in 1,614,104 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000051 ( 0 hom. )
Consequence
TMEM86A
NM_153347.3 missense
NM_153347.3 missense
Scores
4
2
13
Clinical Significance
Conservation
PhyloP100: 6.64
Genes affected
TMEM86A (HGNC:26890): (transmembrane protein 86A) Predicted to enable alkenylglycerophosphocholine hydrolase activity and alkenylglycerophosphoethanolamine hydrolase activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13731337).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TMEM86A | NM_153347.3 | c.518G>A | p.Arg173His | missense_variant | 3/3 | ENST00000280734.3 | NP_699178.1 | |
TMEM86A | XM_047426448.1 | c.518G>A | p.Arg173His | missense_variant | 3/4 | XP_047282404.1 | ||
TMEM86A | XM_047426449.1 | c.518G>A | p.Arg173His | missense_variant | 3/5 | XP_047282405.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TMEM86A | ENST00000280734.3 | c.518G>A | p.Arg173His | missense_variant | 3/3 | 1 | NM_153347.3 | ENSP00000280734 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152210Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
5
AN:
152210
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000995 AC: 25AN: 251160Hom.: 0 AF XY: 0.000133 AC XY: 18AN XY: 135804
GnomAD3 exomes
AF:
AC:
25
AN:
251160
Hom.:
AF XY:
AC XY:
18
AN XY:
135804
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000513 AC: 75AN: 1461776Hom.: 0 Cov.: 31 AF XY: 0.0000605 AC XY: 44AN XY: 727202
GnomAD4 exome
AF:
AC:
75
AN:
1461776
Hom.:
Cov.:
31
AF XY:
AC XY:
44
AN XY:
727202
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74492
GnomAD4 genome
AF:
AC:
5
AN:
152328
Hom.:
Cov.:
32
AF XY:
AC XY:
4
AN XY:
74492
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
14
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 19, 2023 | The c.518G>A (p.R173H) alteration is located in exon 3 (coding exon 3) of the TMEM86A gene. This alteration results from a G to A substitution at nucleotide position 518, causing the arginine (R) at amino acid position 173 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
MutationTaster
Benign
D;D
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
D
Vest4
MutPred
Loss of MoRF binding (P = 0.0274);
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at