Variant 11-102401954-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_052932.3(TMEM123):c.410A>G(p.His137Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,614,076 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

TMEM123
NM_052932.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.378

Variant links:

Genes affected

TMEM123 (HGNC:30138): (transmembrane protein 123) This gene encodes a highly glycosylated transmembrane protein with a high content of threonine and serine residues in its extracellular domain, similar to a broadly defined category of proteins termed mucins. Exposure of some cell types to anti-PORIMIN (pro-oncosis receptor inducing membrane injury) antibody, crosslinks this protein on the cell surface and induces a type of cell death termed oncosis. Oncosis is distinct from apoptosis and is characterized by a loss of cell membrane integrity without DNA fragmentation. This gene product is proposed to function as a cell surface receptor that mediates cell death. [provided by RefSeq, Jul 2008]

TMEM123 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05950129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TMEM123	NM_052932.3 linkuse as main transcript	c.410A>G	p.His137Arg	missense_variant	3/5	ENST00000398136.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TMEM123	ENST00000398136.7 linkuse as main transcript	c.410A>G	p.His137Arg	missense_variant	3/5	1	NM_052932.3	P2	Q8N131-1

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000392

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

GnomAD3 exomes

AF:

0.0000521

AC:

AN:

249424

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

135328

show subpopulations

Gnomad AFR exome

AF:

0.000517

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461852

Hom.:

Cov.:

AF XY:

0.0000179

AC XY:

AN XY:

727224

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.000134

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:

0.0000828

GnomAD4 genome

AF:

0.000210

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.000627

Gnomad4 AMR

AF:

0.000392

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

Alfa

AF:

0.0000436

Hom.:

Bravo

AF:

0.000242

ESP6500AA

AF:

0.000758

AC:

ESP6500EA

AF:

0.000120

AC:

ExAC

AF:

0.0000248

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.80

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.68

T;T;.;T

M_CAP

Benign

0.0057

MetaRNN

Benign

0.060

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-2.4

N;D;D;D

REVEL

Benign

0.017

Sift

Benign

0.12

T;T;T;T

Sift4G

Benign

0.20

T;T;T;T

Polyphen

0.025

B;B;.;.

Vest4

0.18

MVP

0.24

MPC

0.11

ClinPred

0.026

GERP RS

0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.12

gMVP

0.45

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over