Variant rs72558173 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_001384290.1(HLA-G):c.164C>T(p.Thr55Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,613,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0010 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000091 ( 0 hom. )

Consequence

HLA-G
NM_001384290.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.991

Variant links:

Genes affected

HLA-G (HGNC:4964): (major histocompatibility complex, class I, G) HLA-G belongs to the HLA class I heavy chain paralogues. This class I molecule is a heterodimer consisting of a heavy chain and a light chain (beta-2 microglobulin). The heavy chain is anchored in the membrane. HLA-G is expressed on fetal derived placental cells. The heavy chain is approximately 45 kDa and its gene contains 8 exons. Exon one encodes the leader peptide, exons 2 and 3 encode the alpha1 and alpha2 domain, which both bind the peptide, exon 4 encodes the alpha3 domain, exon 5 encodes the transmembrane region, and exon 6 encodes the cytoplasmic tail. [provided by RefSeq, Jul 2008]

HLA-G links:

HLA-G (HGNC:):

HLA-G links:

Genome browser will be placed here

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=0.010911822).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLA-G	NM_001384290.1 linkuse as main transcript	c.164C>T	p.Thr55Met	missense_variant	2/7	ENST00000360323.11	NP_001371219.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLA-G	ENST00000360323.11 linkuse as main transcript	c.164C>T	p.Thr55Met	missense_variant	2/7	6	NM_001384290.1	ENSP00000353472.6		P17693-1

Frequencies

GnomAD3 genomes

AF:

0.00102

AC:

156

AN:

152232

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00352

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

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:

0.000478

GnomAD3 exomes

AF:

0.000255

AC:

AN:

247116

Hom.:

AF XY:

0.000178

AC XY:

AN XY:

134522

show subpopulations

Gnomad AFR exome

AF:

0.00351

Gnomad AMR exome

AF:

0.000261

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:

0.00

GnomAD4 exome

AF:

0.0000910

AC:

133

AN:

1460914

Hom.:

Cov.:

AF XY:

0.0000770

AC XY:

AN XY:

726814

show subpopulations

Gnomad4 AFR exome

AF:

0.00314

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000298

GnomAD4 genome

AF:

0.00102

AC:

156

AN:

152350

Hom.:

Cov.:

AF XY:

0.000953

AC XY:

AN XY:

74500

show subpopulations

Gnomad4 AFR

AF:

0.00351

Gnomad4 AMR

AF:

0.000588

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:

0.000473

Alfa

AF:

0.000336

Hom.:

Bravo

AF:

0.00124

ESP6500AA

AF:

0.00464

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000298

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.023

.;T;T;T;.

Eigen

Benign

-0.052

Eigen_PC

Benign

-0.34

FATHMM_MKL

Benign

0.016

LIST_S2

Benign

0.49

T;T;.;.;T

M_CAP

Benign

0.0016

MetaRNN

Benign

0.011

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Pathogenic

4.1

.;H;H;.;H

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-4.6

D;D;D;D;D

REVEL

Benign

0.061

Sift

Pathogenic

0.0

D;D;D;T;D

Sift4G

Uncertain

0.0080

D;D;D;D;D

Polyphen

1.0

D;D;D;D;.

Vest4

0.24

MVP

0.29

MPC

0.86

ClinPred

0.16

GERP RS

-0.78

Varity_R

0.081

gMVP

0.40

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over