Variant X-84326256-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001177479.2(HDX):c.1869G>A(p.Lys623=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00199 in 1,189,506 control chromosomes in the GnomAD database, including 40 homozygotes. There are 716 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 9 hom., 138 hem., cov: 23)

Exomes 𝑓: 0.0018 ( 31 hom. 578 hem. )

Consequence

HDX
NM_001177479.2 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.222

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant X-84326256-C-T is Benign according to our data. Variant chrX-84326256-C-T is described in ClinVar as [Benign]. Clinvar id is 784565.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.222 with no splicing effect.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00365 (408/111731) while in subpopulation AMR AF= 0.0285 (299/10496). AF 95% confidence interval is 0.0258. There are 9 homozygotes in gnomad4. There are 138 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDX	NM_001177479.2 linkuse as main transcript	c.1869G>A	p.Lys623=	synonymous_variant	10/11	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.1869G>A	p.Lys623=	synonymous_variant	10/11	1	NM_001177479.2	ENSP00000362272	P1	Q7Z353-1
HDX	ENST00000297977.9 linkuse as main transcript	c.1869G>A	p.Lys623=	synonymous_variant	9/10	1		ENSP00000297977	P1	Q7Z353-1
HDX	ENST00000506585.6 linkuse as main transcript	c.1695G>A	p.Lys565=	synonymous_variant	9/10	2		ENSP00000423670		Q7Z353-2

Frequencies

GnomAD3 genomes

AF:

0.00366

AC:

409

AN:

111679

Hom.:

Cov.:

AF XY:

0.00407

AC XY:

138

AN XY:

33885

show subpopulations

Gnomad AFR

AF:

0.00117

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0287

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000169

Gnomad OTH

AF:

0.00464

GnomAD3 exomes

AF:

0.00627

AC:

1136

AN:

181312

Hom.:

AF XY:

0.00401

AC XY:

265

AN XY:

66084

show subpopulations

Gnomad AFR exome

AF:

0.00145

Gnomad AMR exome

AF:

0.0342

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0129

Gnomad SAS exome

AF:

0.0000536

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000247

Gnomad OTH exome

AF:

0.00424

GnomAD4 exome

AF:

0.00182

AC:

1964

AN:

1077775

Hom.:

Cov.:

AF XY:

0.00168

AC XY:

578

AN XY:

344569

show subpopulations

Gnomad4 AFR exome

AF:

0.000923

Gnomad4 AMR exome

AF:

0.0371

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0171

Gnomad4 SAS exome

AF:

0.0000748

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000328

Gnomad4 OTH exome

AF:

0.00216

GnomAD4 genome

AF:

0.00365

AC:

408

AN:

111731

Hom.:

Cov.:

AF XY:

0.00407

AC XY:

138

AN XY:

33947

show subpopulations

Gnomad4 AFR

AF:

0.00117

Gnomad4 AMR

AF:

0.0285

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0161

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000169

Gnomad4 OTH

AF:

0.00458

Alfa

AF:

0.00217

Hom.:

Bravo

AF:

0.00636

EpiCase

AF:

0.000164

EpiControl

AF:

0.00

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

6.2

DANN

Benign

0.61

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