X-84458710-T-G

Variant names:

• chrX-84458710-T-G
• rs5968332
• NM_001177479.2:c.1251+9762A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001177479.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDX	NM_001177479.2	MANE Select	c.1251+9762A>C		intron	N/A	NP_001170950.1	Q7Z353-1
	HDX	NM_144657.5		c.1251+9762A>C		intron	N/A	NP_653258.2
	HDX	NM_001177478.2		c.1077+9762A>C		intron	N/A	NP_001170949.1	Q7Z353-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HDX	ENST00000373177.3	TSL:1 MANE Select	c.1251+9762A>C		intron	N/A	ENSP00000362272.2	Q7Z353-1
	HDX	ENST00000297977.9	TSL:1	c.1251+9762A>C		intron	N/A	ENSP00000297977.5	Q7Z353-1
	HDX	ENST00000851225.1		c.1251+9762A>C		intron	N/A	ENSP00000521284.1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 47823 AN: 110054 Hom.: 7716 Cov.: 22

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

African (AFR) AF: 0.561 AC: 16994 AN: 30297

American (AMR) AF: 0.370 AC: 3842 AN: 10387

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 847 AN: 2629

East Asian (EAS) AF: 0.343 AC: 1180 AN: 3444

South Asian (SAS) AF: 0.543 AC: 1397 AN: 2574

European-Finnish (FIN) AF: 0.456 AC: 2633 AN: 5770

Middle Eastern (MID) AF: 0.227 AC: 49 AN: 216

European-Non Finnish (NFE) AF: 0.383 AC: 20149 AN: 52632

Other (OTH) AF: 0.417 AC: 617 AN: 1481

Alfa AF: 0.384 Hom.: 12178

Bravo AF: 0.429

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.4
DANN	Benign	0.48
PhyloP100		-0.021
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs5968332; hg19: chrX-83713718;