Variant rs62621984 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000366903.8(HLX):c.375A>C(p.Gln125His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0359 in 1,610,232 control chromosomes in the GnomAD database, including 1,277 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.029 ( 84 hom., cov: 34)

Exomes 𝑓: 0.037 ( 1193 hom. )

Consequence

HLX
ENST00000366903.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.00100

Variant links:

Genes affected

HLX (HGNC:4978): (H2.0 like homeobox) Enables sequence-specific DNA binding activity. Predicted to be involved in cell differentiation and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including animal organ development; enteric nervous system development; and regulation of T-helper cell differentiation. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

HLX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0023978949).

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0292 (4440/151802) while in subpopulation NFE AF= 0.0431 (2926/67954). AF 95% confidence interval is 0.0418. There are 84 homozygotes in gnomad4. There are 2113 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 84 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLX	NM_021958.4 linkuse as main transcript	c.375A>C	p.Gln125His	missense_variant	1/4	ENST00000366903.8	NP_068777.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HLX	ENST00000366903.8 linkuse as main transcript	c.375A>C	p.Gln125His	missense_variant	1/4	1	NM_021958.4	ENSP00000355870	P1
HLX	ENST00000549319.2 linkuse as main transcript	n.802A>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4441

AN:

151678

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00761

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0360

Gnomad ASJ

AF:

0.0243

Gnomad EAS

AF:

0.000395

Gnomad SAS

AF:

0.00735

Gnomad FIN

AF:

0.0388

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.0430

Gnomad OTH

AF:

0.0341

GnomAD3 exomes

AF:

0.0311

AC:

7548

AN:

242920

Hom.:

177

AF XY:

0.0313

AC XY:

4138

AN XY:

132020

show subpopulations

Gnomad AFR exome

AF:

0.00701

Gnomad AMR exome

AF:

0.0240

Gnomad ASJ exome

AF:

0.0231

Gnomad EAS exome

AF:

0.000114

Gnomad SAS exome

AF:

0.00719

Gnomad FIN exome

AF:

0.0372

Gnomad NFE exome

AF:

0.0469

Gnomad OTH exome

AF:

0.0425

GnomAD4 exome

AF:

0.0366

AC:

53343

AN:

1458430

Hom.:

1193

Cov.:

AF XY:

0.0362

AC XY:

26262

AN XY:

725406

show subpopulations

Gnomad4 AFR exome

AF:

0.00562

Gnomad4 AMR exome

AF:

0.0242

Gnomad4 ASJ exome

AF:

0.0218

Gnomad4 EAS exome

AF:

0.000127

Gnomad4 SAS exome

AF:

0.00766

Gnomad4 FIN exome

AF:

0.0403

Gnomad4 NFE exome

AF:

0.0418

Gnomad4 OTH exome

AF:

0.0339

GnomAD4 genome

AF:

0.0292

AC:

4440

AN:

151802

Hom.:

Cov.:

AF XY:

0.0285

AC XY:

2113

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.00756

Gnomad4 AMR

AF:

0.0360

Gnomad4 ASJ

AF:

0.0243

Gnomad4 EAS

AF:

0.000396

Gnomad4 SAS

AF:

0.00757

Gnomad4 FIN

AF:

0.0388

Gnomad4 NFE

AF:

0.0431

Gnomad4 OTH

AF:

0.0333

Alfa

AF:

0.0405

Hom.:

Bravo

AF:

0.0292

TwinsUK

AF:

0.0278

AC:

103

ALSPAC

AF:

0.0327

AC:

126

ESP6500AA

AF:

0.00817

AC:

ESP6500EA

AF:

0.0421

AC:

362

ExAC

AF:

0.0312

AC:

3786

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0521

EpiControl

AF:

0.0510

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.69

CADD

Benign

1.9

DANN

Benign

0.51

DEOGEN2

Benign

0.058

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.40

MetaRNN

Benign

0.0024

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.90

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.54

REVEL

Benign

0.087

Sift

Benign

0.047

Sift4G

Uncertain

0.0070

Polyphen

0.88

Vest4

0.36

MutPred

0.16

Loss of helix (P = 0.1299);

MPC

0.43

ClinPred

0.022

GERP RS

-0.054

Varity_R

0.047

gMVP

0.50

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