Variant X-84468904-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001177479.2(HDX):c.819C>T(p.Tyr273=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 1,209,136 control chromosomes in the GnomAD database, including 85 homozygotes. There are 1,160 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.019 ( 50 hom., 557 hem., cov: 22)

Exomes 𝑓: 0.0020 ( 35 hom. 603 hem. )

Consequence

HDX
NM_001177479.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0930

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BP6

Variant X-84468904-G-A is Benign according to our data. Variant chrX-84468904-G-A is described in ClinVar as [Benign]. Clinvar id is 711145.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.093 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0646 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDX	NM_001177479.2 linkuse as main transcript	c.819C>T	p.Tyr273=	synonymous_variant	4/11	ENST00000373177.3	NP_001170950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDX	ENST00000373177.3 linkuse as main transcript	c.819C>T	p.Tyr273=	synonymous_variant	4/11	1	NM_001177479.2	ENSP00000362272	P1	Q7Z353-1

Frequencies

GnomAD3 genomes

AF:

0.0194

AC:

2164

AN:

111730

Hom.:

Cov.:

AF XY:

0.0163

AC XY:

554

AN XY:

33896

show subpopulations

Gnomad AFR

AF:

0.0671

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00702

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000376

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00837

Gnomad NFE

AF:

0.000188

Gnomad OTH

AF:

0.0132

GnomAD3 exomes

AF:

0.00540

AC:

989

AN:

183075

Hom.:

AF XY:

0.00357

AC XY:

241

AN XY:

67559

show subpopulations

Gnomad AFR exome

AF:

0.0677

Gnomad AMR exome

AF:

0.00226

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000220

Gnomad OTH exome

AF:

0.00398

GnomAD4 exome

AF:

0.00200

AC:

2200

AN:

1097354

Hom.:

Cov.:

AF XY:

0.00166

AC XY:

603

AN XY:

362716

show subpopulations

Gnomad4 AFR exome

AF:

0.0670

Gnomad4 AMR exome

AF:

0.00295

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000740

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000159

Gnomad4 OTH exome

AF:

0.00406

GnomAD4 genome

AF:

0.0194

AC:

2167

AN:

111782

Hom.:

Cov.:

AF XY:

0.0164

AC XY:

557

AN XY:

33958

show subpopulations

Gnomad4 AFR

AF:

0.0670

Gnomad4 AMR

AF:

0.00701

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000377

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000188

Gnomad4 OTH

AF:

0.0130

Alfa

AF:

0.00701

Hom.:

Bravo

AF:

0.0221

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	Jul 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

2.5

DANN

Benign

0.52

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