GeneBe

1-225862909-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014698.3(TMEM63A):​c.747-58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,368,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 30)
Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

TMEM63A
NM_014698.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.04

Publications

9 publications found
Variant links:
Genes affected
TMEM63A (HGNC:29118): (transmembrane protein 63A) Enables mechanosensitive ion channel activity. Predicted to be involved in cation transmembrane transport. Located in centriolar satellite and lysosomal membrane. Implicated in hypomyelinating leukodystrophy. [provided by Alliance of Genome Resources, Apr 2022]
TMEM63A Gene-Disease associations (from GenCC):
  • leukodystrophy, hypomyelinating, 19, transient infantile
    Inheritance: AD Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM63ANM_014698.3 linkc.747-58G>A intron_variant Intron 10 of 24 ENST00000366835.8 NP_055513.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM63AENST00000366835.8 linkc.747-58G>A intron_variant Intron 10 of 24 1 NM_014698.3 ENSP00000355800.3
TMEM63AENST00000537914.5 linkc.-232-58G>A intron_variant Intron 3 of 6 1 ENSP00000445237.1
TMEM63AENST00000474478.5 linkn.2456G>A non_coding_transcript_exon_variant Exon 2 of 4 2
TMEM63AENST00000483779.1 linkn.515-58G>A intron_variant Intron 1 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
30
GnomAD4 exome
AF:
0.00000146
AC:
2
AN:
1368462
Hom.:
0
Cov.:
22
AF XY:
0.00000293
AC XY:
2
AN XY:
681538
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31342
American (AMR)
AF:
0.00
AC:
0
AN:
39268
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25064
East Asian (EAS)
AF:
0.00
AC:
0
AN:
37530
South Asian (SAS)
AF:
0.00
AC:
0
AN:
81044
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
51264
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5622
European-Non Finnish (NFE)
AF:
0.00000192
AC:
2
AN:
1040152
Other (OTH)
AF:
0.00
AC:
0
AN:
57176
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
30
Alfa
AF:
0.00
Hom.:
4382

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.043
DANN
Benign
0.88
PhyloP100
-2.0
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs10158985; hg19: chr1-226050609; API