X-84458710-T-G

Position:

• chrX-84458710-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001177479.2(HDX):​c.1251+9762A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 110,102 control chromosomes in the GnomAD database, including 7,716 homozygotes. There are 13,860 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.43 (7716 hom., 13860 hem., cov: 22)
• Consequence: HDX NM_001177479.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0210

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDX	NM_001177479.2	c.1251+9762A>C		intron_variant		ENST00000373177.3	NP_001170950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDX	ENST00000373177.3	c.1251+9762A>C		intron_variant		1	NM_001177479.2	ENSP00000362272.2
HDX	ENST00000297977.9	c.1251+9762A>C		intron_variant		1		ENSP00000297977.5
HDX	ENST00000506585.6	c.1077+9762A>C		intron_variant		2		ENSP00000423670.2
HDX	ENST00000472135.2	n.1105+9762A>C		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.435 AC: 47823 AN: 110054 Hom.: 7716 Cov.: 22 AF XY: 0.427 AC XY: 13836 AN XY: 32372

Gnomad AFR AF: 0.561

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.370

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.342

Gnomad SAS AF: 0.547

Gnomad FIN AF: 0.456

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.419

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.435 AC: 47845 AN: 110102 Hom.: 7716 Cov.: 22 AF XY: 0.427 AC XY: 13860 AN XY: 32430

Gnomad4 AFR AF: 0.561

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.322

Gnomad4 EAS AF: 0.343

Gnomad4 SAS AF: 0.543

Gnomad4 FIN AF: 0.456

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.417

Alfa AF: 0.367 Hom.: 7405

Bravo AF: 0.429

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.48

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

Other links and lift over

dbSNP: rs5968332; hg19: chrX-83713718;