dbSNP rs1326672438: TMEM143:p.Gly435Ala (chr19-48333295-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_018273.4(TMEM143):c.1304G>C(p.Gly435Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000507 in 1,578,536 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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

TMEM143
NM_018273.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.901

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:

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 (MetaRNN=0.0596281).

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.1304G>C	p.Gly435Ala	missense	Exon 8 of 8	NP_060743.2
TMEM143	NM_001303538.2		c.1199G>C	p.Gly400Ala	missense	Exon 7 of 7	NP_001290467.1	B4DMT0
TMEM143	NM_001303539.2		c.1109G>C	p.Gly370Ala	missense	Exon 7 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.1304G>C	p.Gly435Ala	missense	Exon 8 of 8	ENSP00000293261.2	Q96AN5-1
TMEM143	ENST00000377431.6	TSL:1	c.1004G>C	p.Gly335Ala	missense	Exon 6 of 6	ENSP00000366649.1	Q96AN5-2
TMEM143	ENST00000948722.1		c.1301G>C	p.Gly434Ala	missense	Exon 8 of 8	ENSP00000618781.1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000427

AC:

AN:

234086

AF XY:

0.00000787

show subpopulations

Gnomad AFR exome

AF:

0.0000633

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:

0.00000491

AC:

AN:

1426452

Hom.:

Cov.:

AF XY:

0.00000283

AC XY:

AN XY:

707722

show subpopulations

African (AFR)

AF:

0.0000613

AC:

AN:

32608

American (AMR)

AF:

0.00

AC:

AN:

41424

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24688

East Asian (EAS)

AF:

0.00

AC:

AN:

38830

South Asian (SAS)

AF:

0.00

AC:

AN:

83160

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52368

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5622

European-Non Finnish (NFE)

AF:

0.00000275

AC:

AN:

1089336

Other (OTH)

AF:

0.0000342

AC:

AN:

58416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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

AF:

0.00000658

AC:

AN:

152084

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74296

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41412

American (AMR)

AF:

0.00

AC:

AN:

15242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

0.077

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

Eigen

Benign

-0.50

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.027

LIST_S2

Uncertain

0.87

M_CAP

Benign

0.0058

MetaRNN

Benign

0.060

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PhyloP100

0.90

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.58

REVEL

Benign

0.014

Sift

Benign

0.39

Sift4G

Benign

0.46

Polyphen

0.52

Vest4

0.19

MutPred

0.27

Gain of glycosylation at P433 (P = 0.1432)

MVP

0.14

MPC

0.89

ClinPred

0.095

GERP RS

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

Varity_R

0.079

gMVP

0.27

Mutation Taster

=96/4

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over