Variant rs10947368 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002119.4(HLA-DOA):c.360G>C(p.Lys120Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,276 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. Synonymous variant affecting the same amino acid position (i.e. K120K) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HLA-DOA
NM_002119.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.471

Variant links:

Genes affected

HLA-DOA (HGNC:4936): (major histocompatibility complex, class II, DO alpha) HLA-DOA belongs to the HLA class II alpha chain paralogues. HLA-DOA forms a heterodimer with HLA-DOB. The heterodimer, HLA-DO, is found in lysosomes in B cells and regulates HLA-DM-mediated peptide loading on MHC class II molecules. In comparison with classical HLA class II molecules, this gene exhibits very little sequence variation, especially at the protein level. [provided by RefSeq, Jul 2008]

HLA-DOA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27906775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HLA-DOA	NM_002119.4 linkuse as main transcript	c.360G>C	p.Lys120Asn	missense_variant	3/5	ENST00000229829.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Appris
HLA-DOA	ENST00000229829.7 linkuse as main transcript	c.360G>C	p.Lys120Asn	missense_variant	3/5	NM_002119.4	P1
HLA-DOA	ENST00000374813.1 linkuse as main transcript	c.193G>C	p.Val65Leu	missense_variant	3/3
HLA-DOA	ENST00000485901.1 linkuse as main transcript	n.71G>C		non_coding_transcript_exon_variant	2/3
HLA-DOA	ENST00000495532.1 linkuse as main transcript	n.426G>C		non_coding_transcript_exon_variant	2/2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152164

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

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

GnomAD3 exomes

AF:

0.00000815

AC:

AN:

245516

Hom.:

AF XY:

0.00000747

AC XY:

AN XY:

133830

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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:

0.00000205

AC:

AN:

1460276

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726418

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152164

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74334

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.59

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.19

Eigen

Benign

0.14

Eigen_PC

Benign

0.099

FATHMM_MKL

Benign

0.19

M_CAP

Benign

0.0086

MetaRNN

Benign

0.28

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.6

MutationTaster

Benign

0.55

P;P

PrimateAI

Benign

0.38

PROVEAN

Uncertain

-2.9

REVEL

Benign

0.12

Sift

Benign

0.16

Sift4G

Benign

0.17

Polyphen

1.0

Vest4

0.29

MutPred

0.58

Loss of ubiquitination at K120 (P = 0.0446);

MVP

0.32

MPC

0.85

ClinPred

0.91

GERP RS

4.5

Varity_R

0.29

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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