Variant rs11578466 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021958.4(HLX):c.1160C>G(p.Ala387Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.131 in 1,613,906 control chromosomes in the GnomAD database, including 15,283 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.12 ( 1211 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14072 hom. )

Consequence

HLX
NM_021958.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.504

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:

ENSG00000286231 (HGNC:):

ENSG00000286231 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=0.0012665093).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HLX	NM_021958.4 linkuse as main transcript	c.1160C>G	p.Ala387Gly	missense_variant	4/4	ENST00000366903.8	NP_068777.1	Q14774

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
HLX	ENST00000366903.8 linkuse as main transcript	c.1160C>G	p.Ala387Gly	missense_variant	4/4	1	NM_021958.4	ENSP00000355870.5	Q14774
ENSG00000286231	ENST00000651706.1 linkuse as main transcript	n.*468C>G		non_coding_transcript_exon_variant	9/9			ENSP00000499157.1	A0A494C1P3
ENSG00000286231	ENST00000651706.1 linkuse as main transcript	n.*468C>G		3_prime_UTR_variant	9/9			ENSP00000499157.1	A0A494C1P3

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17975

AN:

152014

Hom.:

1212

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0779

Gnomad AMI

AF:

0.0779

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0533

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.149

Gnomad OTH

AF:

0.143

GnomAD3 exomes

AF:

0.119

AC:

29826

AN:

249994

Hom.:

2237

AF XY:

0.121

AC XY:

16411

AN XY:

135238

show subpopulations

Gnomad AFR exome

AF:

0.0766

Gnomad AMR exome

AF:

0.111

Gnomad ASJ exome

AF:

0.220

Gnomad EAS exome

AF:

0.000381

Gnomad SAS exome

AF:

0.0646

Gnomad FIN exome

AF:

0.111

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.167

GnomAD4 exome

AF:

0.132

AC:

192697

AN:

1461774

Hom.:

14072

Cov.:

AF XY:

0.131

AC XY:

95398

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0808

Gnomad4 AMR exome

AF:

0.113

Gnomad4 ASJ exome

AF:

0.216

Gnomad4 EAS exome

AF:

0.000428

Gnomad4 SAS exome

AF:

0.0674

Gnomad4 FIN exome

AF:

0.114

Gnomad4 NFE exome

AF:

0.142

Gnomad4 OTH exome

AF:

0.141

GnomAD4 genome

AF:

0.118

AC:

17976

AN:

152132

Hom.:

1211

Cov.:

AF XY:

0.114

AC XY:

8514

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0779

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.226

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.0534

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.149

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.124

Hom.:

514

Bravo

AF:

0.121

TwinsUK

AF:

0.141

AC:

522

ALSPAC

AF:

0.124

AC:

478

ESP6500AA

AF:

0.0797

AC:

351

ESP6500EA

AF:

0.150

AC:

1287

ExAC

AF:

0.118

AC:

14388

Asia WGS

AF:

0.0350

AC:

121

AN:

3478

EpiCase

AF:

0.171

EpiControl

AF:

0.172

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.10

T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.29

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.67

T;T

MetaRNN

Benign

0.0013

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

L;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-0.77

N;N

REVEL

Benign

0.075

Sift

Benign

0.096

T;T

Sift4G

Benign

0.23

T;T

Polyphen

0.012

B;.

Vest4

0.072

MPC

0.60

ClinPred

0.0074

GERP RS

3.2

Varity_R

0.059

gMVP

0.19

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