Variant 19-48334172-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_018273.4(TMEM143):c.1001A>G(p.Gln334Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,453,280 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

TMEM143
NM_018273.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.49

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:

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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=0.26086277).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM143	NM_018273.4 link	c.1001A>G	p.Gln334Arg	missense_variant	7/8	ENST00000293261.8	NP_060743.2	Q96AN5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TMEM143	ENST00000293261.8 link	c.1001A>G	p.Gln334Arg	missense_variant	7/8	1	NM_018273.4	ENSP00000293261.2	Q96AN5-1
TMEM143	ENST00000377431.6 link	c.701A>G	p.Gln234Arg	missense_variant	5/6	1		ENSP00000366649.1	Q96AN5-2
TMEM143	ENST00000435956.7 link	c.896A>G	p.Gln299Arg	missense_variant	6/7	2		ENSP00000397038.2	B4DMT0
TMEM143	ENST00000600816.1 link	n.488A>G		non_coding_transcript_exon_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453280

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722262

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:

0.0000117

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

May 05, 2023

The c.1001A>G (p.Q334R) alteration is located in exon 7 (coding exon 7) of the TMEM143 gene. This alteration results from a A to G substitution at nucleotide position 1001, causing the glutamine (Q) at amino acid position 334 to be replaced by an arginine (R). 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

0.11

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

T;.;T

Eigen

Benign

-0.0065

Eigen_PC

Benign

0.0040

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.78

T;T;T

M_CAP

Benign

0.025

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.3

L;.;.

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.90

N;N;N

REVEL

Benign

0.17

Sift

Benign

0.31

T;T;T

Sift4G

Benign

0.18

T;T;T

Polyphen

0.78

P;P;P

Vest4

0.42

MutPred

0.57

Gain of MoRF binding (P = 0.0106);.;.;

MVP

0.21

MPC

0.85

ClinPred

0.47

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.16

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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