rs752941604

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chrX-84440548-C-A
• chrX-84440548-C-T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3 BS2

The NM_001177479.2(HDX):​c.1289G>T​(p.Cys430Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000288 in 1,181,118 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000021 (0 hom. 6 hem.)
• Consequence: HDX NM_001177479.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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: Likely_benign. The variant received -3 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.758
• BS2: High Hemizygotes in GnomAdExome4 at 6 gene

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>T	p.Cys430Phe	missense	Exon 5 of 11	NP_001170950.1	Q7Z353-1
	HDX	NM_144657.5		c.1289G>T	p.Cys430Phe	missense	Exon 4 of 10	NP_653258.2
	HDX	NM_001177478.2		c.1115G>T	p.Cys372Phe	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>T	p.Cys430Phe	missense	Exon 5 of 11	ENSP00000362272.2	Q7Z353-1
	HDX	ENST00000297977.9	TSL:1	c.1289G>T	p.Cys430Phe	missense	Exon 4 of 10	ENSP00000297977.5	Q7Z353-1
	HDX	ENST00000851225.1		c.1289G>T	p.Cys430Phe	missense	Exon 5 of 11	ENSP00000521284.1

Frequencies

GnomAD3 genomes AF: 0.0000990 AC: 11 AN: 111103 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000171 AC: 3 AN: 175663 AF XY: 0.0000164

Gnomad AFR exome AF: 0.0000791

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000253

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000215 AC: 23 AN: 1070015 Hom.: 0 Cov.: 24 AF XY: 0.0000176 AC XY: 6 AN XY: 340685

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: 52847

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: 0.0000257 AC: 21 AN: 818669

Other (OTH) AF: 0.0000443 AC: 2 AN: 45115

GnomAD4 genome AF: 0.0000990 AC: 11 AN: 111103 Hom.: 0 Cov.: 23 AF XY: 0.0000299 AC XY: 1 AN XY: 33445

African (AFR) AF: 0.000131 AC: 4 AN: 30646

American (AMR) AF: 0.00 AC: 0 AN: 10394

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 3553

South Asian (SAS) AF: 0.00 AC: 0 AN: 2675

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.000133 AC: 7 AN: 52773

Other (OTH) AF: 0.00 AC: 0 AN: 1494

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000680

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	0.11
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.50	D
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.028	D
MetaRNN	Pathogenic	0.76	D
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.7
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0070	D
Sift4G	Uncertain	0.043	D
Polyphen		0.99	D
Vest4		0.80
MVP		0.72
MPC		0.66
ClinPred		0.60	D
GERP RS		5.4
Varity_R		0.73
gMVP		0.47
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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;