Variant X-84469146-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001177479.2(HDX):c.577G>A(p.Ala193Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00246 in 1,207,591 control chromosomes in the GnomAD database, including 58 homozygotes. There are 750 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.013 ( 34 hom., 375 hem., cov: 23)

Exomes 𝑓: 0.0014 ( 24 hom. 375 hem. )

Consequence

HDX
NM_001177479.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.401

Variant links:

Genes affected

HDX (HGNC:26411): (highly divergent homeobox) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

HDX links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001996249).

BP6

Variant X-84469146-C-T is Benign according to our data. Variant chrX-84469146-C-T is described in ClinVar as [Benign]. Clinvar id is 777796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0132 (1477/111705) while in subpopulation AFR AF= 0.0467 (1435/30723). AF 95% confidence interval is 0.0447. There are 34 homozygotes in gnomad4. There are 375 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 34 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDX	NM_001177479.2 linkuse as main transcript	c.577G>A	p.Ala193Thr	missense_variant	4/11	ENST00000373177.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDX	ENST00000373177.3 linkuse as main transcript	c.577G>A	p.Ala193Thr	missense_variant	4/11	1	NM_001177479.2	P1	Q7Z353-1

Frequencies

GnomAD3 genomes

AF:

0.0132

AC:

1472

AN:

111649

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

371

AN XY:

33851

show subpopulations

Gnomad AFR

AF:

0.0466

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00257

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:

0.0000752

Gnomad OTH

AF:

0.00730

GnomAD3 exomes

AF:

0.00394

AC:

714

AN:

181078

Hom.:

AF XY:

0.00284

AC XY:

187

AN XY:

65834

show subpopulations

Gnomad AFR exome

AF:

0.0489

Gnomad AMR exome

AF:

0.00214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000987

Gnomad OTH exome

AF:

0.00135

GnomAD4 exome

AF:

0.00136

AC:

1491

AN:

1095886

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

375

AN XY:

361422

show subpopulations

Gnomad4 AFR exome

AF:

0.0474

Gnomad4 AMR exome

AF:

0.00237

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000744

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000369

Gnomad4 OTH exome

AF:

0.00259

GnomAD4 genome

AF:

0.0132

AC:

1477

AN:

111705

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

375

AN XY:

33917

show subpopulations

Gnomad4 AFR

AF:

0.0467

Gnomad4 AMR

AF:

0.00257

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000752

Gnomad4 OTH

AF:

0.00721

Alfa

AF:

0.00141

Hom.:

Bravo

AF:

0.0146

ESP6500AA

AF:

0.0477

AC:

183

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00440

AC:

534

EpiCase

AF:

0.000109

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 16, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.054

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.90

CADD

Benign

6.1

DANN

Benign

0.22

DEOGEN2

Benign

0.024

T;.;T;.

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.31

.;T;T;T

MetaRNN

Benign

0.0020

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.74

N;.;N;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.60

N;.;.;N

REVEL

Benign

0.023

Sift

Benign

1.0

T;.;.;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.0

B;.;B;.

Vest4

0.11

MVP

0.12

MPC

0.12

ClinPred

0.0043

GERP RS

2.3

Varity_R

0.038

gMVP

0.12

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over