Variant 7-143286019-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001282876.2(TMEM139):c.62C>G(p.Ser21Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

TMEM139
NM_001282876.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.17

Variant links:

Genes affected

TMEM139 (HGNC:22058): (transmembrane protein 139) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

TMEM139 links:

TMEM139 (HGNC:):

TMEM139 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMEM139	NM_001282876.2 linkuse as main transcript	c.62C>G	p.Ser21Cys	missense_variant	2/3	ENST00000359333.8	NP_001269805.1	Q8IV31

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMEM139	ENST00000359333.8 linkuse as main transcript	c.62C>G	p.Ser21Cys	missense_variant	2/3	1	NM_001282876.2	ENSP00000352284.3		Q8IV31

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Jul 17, 2024

The c.62C>G (p.S21C) alteration is located in exon 4 (coding exon 1) of the TMEM139 gene. This alteration results from a C to G substitution at nucleotide position 62, causing the serine (S) at amino acid position 21 to be replaced by a cysteine (C). 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

-0.018

BayesDel_noAF

Benign

-0.26

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.098

T;T;T;T;T

Eigen

Benign

0.093

Eigen_PC

Benign

0.022

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.67

.;.;.;.;T

M_CAP

Benign

0.0038

MetaRNN

Uncertain

0.46

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Uncertain

2.2

M;M;M;M;M

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-3.7

D;D;D;D;D

REVEL

Benign

0.11

Sift

Uncertain

0.021

D;D;D;D;D

Sift4G

Uncertain

0.057

T;T;T;T;T

Polyphen

1.0

D;D;D;D;D

Vest4

0.52

MutPred

0.43

Loss of catalytic residue at L17 (P = 0.1669);Loss of catalytic residue at L17 (P = 0.1669);Loss of catalytic residue at L17 (P = 0.1669);Loss of catalytic residue at L17 (P = 0.1669);Loss of catalytic residue at L17 (P = 0.1669);

MVP

0.067

MPC

0.40

ClinPred

0.98

GERP RS

3.2

Varity_R

0.17

gMVP

0.86

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