X-103713618-C-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_182541.2(TMEM31):c.127C>A(p.Gln43Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000107 in 1,210,566 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000053 ( 0 hom., 2 hem., cov: 23)
Exomes 𝑓: 0.0000064 ( 0 hom. 3 hem. )
Consequence
TMEM31
NM_182541.2 missense
NM_182541.2 missense
Scores
3
6
7
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
TMEM31 (HGNC:28601): (transmembrane protein 31) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]
GLRA4 (HGNC:31715): (glycine receptor alpha 4 (pseudogene)) This gene encodes a glycine receptor and member of the ligand-gated ion channel family of proteins. The encoded protein is missing the fourth transmembrane region compared to related proteins in mouse and rat, and experimental data suggests that the human protein is functionally inactive. However, there is strong evidence to support transcription of this gene. As a result, RefSeq, in collaboration with Ensembl-GENCODE, has determined that this locus is best described as a transcribed pseudogene. [provided by RefSeq, Aug 2019]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.20409682).
BS2
High Hemizygotes in GnomAd4 at 2 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TMEM31 | NM_182541.2 | c.127C>A | p.Gln43Lys | missense_variant | 3/3 | ENST00000319560.7 | |
GLRA4 | NR_164162.1 | n.1277G>T | non_coding_transcript_exon_variant | 8/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TMEM31 | ENST00000319560.7 | c.127C>A | p.Gln43Lys | missense_variant | 3/3 | 1 | NM_182541.2 | P1 | |
GLRA4 | ENST00000674183.1 | n.985G>T | non_coding_transcript_exon_variant | 8/9 | |||||
ENST00000674243.1 | n.1406G>T | non_coding_transcript_exon_variant | 8/9 | ||||||
ENST00000436213.5 | n.1499G>T | non_coding_transcript_exon_variant | 7/8 | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000534 AC: 6AN: 112300Hom.: 0 Cov.: 23 AF XY: 0.0000580 AC XY: 2AN XY: 34458
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GnomAD3 exomes AF: 0.0000109 AC: 2AN: 183512Hom.: 0 AF XY: 0.0000294 AC XY: 2AN XY: 67944
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GnomAD4 exome AF: 0.00000637 AC: 7AN: 1098266Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 3AN XY: 363620
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GnomAD4 genome AF: 0.0000534 AC: 6AN: 112300Hom.: 0 Cov.: 23 AF XY: 0.0000580 AC XY: 2AN XY: 34458
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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 | Mar 04, 2024 | The c.127C>A (p.Q43K) alteration is located in exon 3 (coding exon 2) of the TMEM31 gene. This alteration results from a C to A substitution at nucleotide position 127, causing the glutamine (Q) at amino acid position 43 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T
M_CAP
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at