NM_001177479.2:c.1289G>A

Variant names:

• chrX-84440548-C-T
• rs752941604
• NM_001177479.2:c.1289G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001177479.2(HDX):​c.1289G>A​(p.Cys430Tyr) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 111,153 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C430F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000018 (0 hom., 0 hem., cov: 23)
  • Exomes 𝑓: 0.0 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: HDX NM_001177479.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.69
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.1289G>A	p.Cys430Tyr	missense	Exon 5 of 11	NP_001170950.1	Q7Z353-1
	HDX	NM_144657.5		c.1289G>A	p.Cys430Tyr	missense	Exon 4 of 10	NP_653258.2
	HDX	NM_001177478.2		c.1115G>A	p.Cys372Tyr	missense	Exon 4 of 10	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.1289G>A	p.Cys430Tyr	missense	Exon 5 of 11	ENSP00000362272.2	Q7Z353-1
	HDX	ENST00000297977.9	TSL:1	c.1289G>A	p.Cys430Tyr	missense	Exon 4 of 10	ENSP00000297977.5	Q7Z353-1
	HDX	ENST00000851225.1		c.1289G>A	p.Cys430Tyr	missense	Exon 5 of 11	ENSP00000521284.1

Frequencies

GnomAD3 genomes AF: 0.0000180 AC: 2 AN: 111103 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000563

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000569 AC: 1 AN: 175663 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000759

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1070010 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 340680

African (AFR) AF: 0.00 AC: 0 AN: 25627

American (AMR) AF: 0.00 AC: 0 AN: 34538

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19091

East Asian (EAS) AF: 0.00 AC: 0 AN: 29823

South Asian (SAS) AF: 0.00 AC: 0 AN: 52846

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40344

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3961

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 818665

Other (OTH) AF: 0.00 AC: 0 AN: 45115

GnomAD4 genome AF: 0.0000180 AC: 2 AN: 111153 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 33505

African (AFR) AF: 0.00 AC: 0 AN: 30713

American (AMR) AF: 0.00 AC: 0 AN: 10407

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2647

East Asian (EAS) AF: 0.000565 AC: 2 AN: 3542

South Asian (SAS) AF: 0.00 AC: 0 AN: 2665

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5997

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52766

Other (OTH) AF: 0.00 AC: 0 AN: 1513

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Uncertain	0.91	D
M_CAP	Benign	0.021	T
MetaRNN	Uncertain	0.70	D
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.7
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.8	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.011	D
Sift4G	Benign	0.081	T
Polyphen		0.99	D
Vest4		0.79
MutPred		0.47		Gain of MoRF binding (P = 0.0683)
MVP		0.67
MPC		0.69
ClinPred		0.81	D
GERP RS		5.4
Varity_R		0.55
gMVP		0.50
Mutation Taster		=87/13	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs752941604; hg19: chrX-83695556;