Variant 19-48333373-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018273.4(TMEM143):c.1226A>C(p.Glu409Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000659 in 1,608,676 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000071 ( 3 hom. )

Consequence

TMEM143
NM_018273.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.884

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]

TMEM143 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015444219).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM143	NM_018273.4 linkuse as main transcript	c.1226A>C	p.Glu409Ala	missense_variant	8/8	ENST00000293261.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM143	ENST00000293261.8 linkuse as main transcript	c.1226A>C	p.Glu409Ala	missense_variant	8/8	1	NM_018273.4	P1	Q96AN5-1
TMEM143	ENST00000377431.6 linkuse as main transcript	c.926A>C	p.Glu309Ala	missense_variant	6/6	1			Q96AN5-2
TMEM143	ENST00000435956.7 linkuse as main transcript	c.1121A>C	p.Glu374Ala	missense_variant	7/7	2
TMEM143	ENST00000600816.1 linkuse as main transcript	n.713A>C		non_coding_transcript_exon_variant	3/3	2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000137

AC:

AN:

247414

Hom.:

AF XY:

0.000172

AC XY:

AN XY:

133946

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000707

AC:

103

AN:

1456412

Hom.:

Cov.:

AF XY:

0.0000939

AC XY:

AN XY:

724548

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00111

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.000100

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.00000756

ExAC

AF:

0.000115

AC:

Asia WGS

AF:

0.000577

AC:

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

Jun 24, 2022

The c.1226A>C (p.E409A) alteration is located in exon 8 (coding exon 8) of the TMEM143 gene. This alteration results from a A to C substitution at nucleotide position 1226, causing the glutamic acid (E) at amino acid position 409 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.055

T;.;T

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.0038

MetaRNN

Benign

0.015

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.3

N;N;N

REVEL

Benign

0.020

Sift

Benign

0.23

T;T;T

Sift4G

Benign

0.33

T;T;T

Polyphen

0.0

B;B;B

Vest4

0.059

MutPred

0.23

Gain of MoRF binding (P = 0.0683);.;.;

MVP

0.20

MPC

0.82

ClinPred

0.051

GERP RS

2.3

Varity_R

0.099

gMVP

0.20

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over