Genetic Variant TMEM143:p.Gln334Arg (chr19-48334172-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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. 15/22 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

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26086277).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018273.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM143	NM_018273.4	MANE Select	c.1001A>G	p.Gln334Arg	missense	Exon 7 of 8	NP_060743.2
TMEM143	NM_001303538.2		c.896A>G	p.Gln299Arg	missense	Exon 6 of 7	NP_001290467.1	B4DMT0
TMEM143	NM_001303539.2		c.806A>G	p.Gln269Arg	missense	Exon 6 of 7	NP_001290468.1	B4DPF8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
TMEM143	ENST00000293261.8	TSL:1 MANE Select	c.1001A>G	p.Gln334Arg	missense	Exon 7 of 8	ENSP00000293261.2	Q96AN5-1
TMEM143	ENST00000377431.6	TSL:1	c.701A>G	p.Gln234Arg	missense	Exon 5 of 6	ENSP00000366649.1	Q96AN5-2
TMEM143	ENST00000948722.1		c.998A>G	p.Gln333Arg	missense	Exon 7 of 8	ENSP00000618781.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

228444

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1453280

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722262

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33320

American (AMR)

AF:

0.00

AC:

AN:

44118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25884

East Asian (EAS)

AF:

0.00

AC:

AN:

39448

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50942

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5712

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108566

Other (OTH)

AF:

0.00

AC:

AN:

60034

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.035

Eigen

Benign

-0.0065

Eigen_PC

Benign

0.0040

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.78

M_CAP

Benign

0.025

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.3

PhyloP100

2.5

PrimateAI

Benign

0.48

PROVEAN

Benign

-0.90

REVEL

Benign

0.17

Sift

Benign

0.31

Sift4G

Benign

0.18

Polyphen

0.78

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

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over