19-48333295-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018273.4(TMEM143):​c.1304G>A​(p.Gly435Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000021 in 1,426,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G435A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

TMEM143
NM_018273.4 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.901
Variant links:
Genes affected
TMEM143 (HGNC:25603): (transmembrane protein 143) Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Located in mitochondrion. [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=0.07611853).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TMEM143NM_018273.4 linkc.1304G>A p.Gly435Asp missense_variant Exon 8 of 8 ENST00000293261.8 NP_060743.2 Q96AN5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TMEM143ENST00000293261.8 linkc.1304G>A p.Gly435Asp missense_variant Exon 8 of 8 1 NM_018273.4 ENSP00000293261.2 Q96AN5-1
TMEM143ENST00000377431.6 linkc.1004G>A p.Gly335Asp missense_variant Exon 6 of 6 1 ENSP00000366649.1 Q96AN5-2
TMEM143ENST00000435956.7 linkc.1199G>A p.Gly400Asp missense_variant Exon 7 of 7 2 ENSP00000397038.2 B4DMT0
TMEM143ENST00000600816.1 linkn.791G>A non_coding_transcript_exon_variant Exon 3 of 3 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000210
AC:
3
AN:
1426452
Hom.:
0
Cov.:
30
AF XY:
0.00000424
AC XY:
3
AN XY:
707722
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000258
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.18e-7
Gnomad4 OTH exome
AF:
0.0000171
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.015
T;.;T
Eigen
Benign
-0.49
Eigen_PC
Benign
-0.49
FATHMM_MKL
Benign
0.019
N
LIST_S2
Benign
0.72
T;T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.076
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L;.;.
PrimateAI
Benign
0.46
T
PROVEAN
Benign
-0.64
N;N;N
REVEL
Benign
0.022
Sift
Benign
0.11
T;T;T
Sift4G
Benign
0.30
T;T;T
Polyphen
0.52
P;P;P
Vest4
0.15
MutPred
0.28
Gain of solvent accessibility (P = 0.0638);.;.;
MVP
0.17
MPC
1.0
ClinPred
0.45
T
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.6
Varity_R
0.11
gMVP
0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-48836552; COSMIC: COSV99507139; COSMIC: COSV99507139; API