Variant rs12141189 details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000366903.8(HLX):c.346T>C(p.Ser116Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 1,612,368 control chromosomes in the GnomAD database, including 47,317 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 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 0.23 ( 4161 hom., cov: 33)

Exomes 𝑓: 0.24 ( 43156 hom. )

Consequence

HLX
ENST00000366903.8 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.02

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=0.001368612).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.249 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.346T>C	p.Ser116Pro	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.346T>C	p.Ser116Pro	missense_variant	1/4	1	NM_021958.4	ENSP00000355870	P1
HLX	ENST00000549319.2 linkuse as main transcript	n.773T>C		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

34929

AN:

151988

Hom.:

4153

Cov.:

show subpopulations

Gnomad AFR

AF:

0.188

Gnomad AMI

AF:

0.300

Gnomad AMR

AF:

0.255

Gnomad ASJ

AF:

0.176

Gnomad EAS

AF:

0.218

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.313

Gnomad MID

AF:

0.191

Gnomad NFE

AF:

0.242

Gnomad OTH

AF:

0.218

GnomAD3 exomes

AF:

0.244

AC:

59203

AN:

242226

Hom.:

7632

AF XY:

0.238

AC XY:

31515

AN XY:

132336

show subpopulations

Gnomad AFR exome

AF:

0.187

Gnomad AMR exome

AF:

0.326

Gnomad ASJ exome

AF:

0.174

Gnomad EAS exome

AF:

0.229

Gnomad SAS exome

AF:

0.200

Gnomad FIN exome

AF:

0.306

Gnomad NFE exome

AF:

0.237

Gnomad OTH exome

AF:

0.229

GnomAD4 exome

AF:

0.240

AC:

350889

AN:

1460262

Hom.:

43156

Cov.:

AF XY:

0.238

AC XY:

172835

AN XY:

726452

show subpopulations

Gnomad4 AFR exome

AF:

0.182

Gnomad4 AMR exome

AF:

0.317

Gnomad4 ASJ exome

AF:

0.176

Gnomad4 EAS exome

AF:

0.195

Gnomad4 SAS exome

AF:

0.196

Gnomad4 FIN exome

AF:

0.306

Gnomad4 NFE exome

AF:

0.243

Gnomad4 OTH exome

AF:

0.229

GnomAD4 genome

AF:

0.230

AC:

34958

AN:

152106

Hom.:

4161

Cov.:

AF XY:

0.234

AC XY:

17369

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.188

Gnomad4 AMR

AF:

0.256

Gnomad4 ASJ

AF:

0.176

Gnomad4 EAS

AF:

0.218

Gnomad4 SAS

AF:

0.196

Gnomad4 FIN

AF:

0.313

Gnomad4 NFE

AF:

0.242

Gnomad4 OTH

AF:

0.214

Alfa

AF:

0.231

Hom.:

1799

Bravo

AF:

0.226

ESP6500AA

AF:

0.193

AC:

846

ESP6500EA

AF:

0.222

AC:

1904

ExAC

AF:

0.233

AC:

28129

Asia WGS

AF:

0.184

AC:

639

AN:

3472

EpiCase

AF:

0.230

EpiControl

AF:

0.227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.5

MutationTaster

Benign

0.18

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.3

REVEL

Benign

0.028

Sift

Benign

0.086

Sift4G

Benign

0.36

Polyphen

0.048

Vest4

0.065

MPC

0.58

ClinPred

0.0053

GERP RS

3.4

Varity_R

0.25

gMVP

0.47

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