X-84326256-C-T

Variant names:

• chrX-84326256-C-T
• rs143487849
• NM_001177479.2:c.1869G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001177479.2(HDX):​c.1869G>A​(p.Lys623Lys) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.222
• 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 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.1869G>A	p.Lys623Lys	synonymous	Exon 10 of 11	NP_001170950.1	Q7Z353-1
	HDX	NM_144657.5		c.1869G>A	p.Lys623Lys	synonymous	Exon 9 of 10	NP_653258.2
	HDX	NM_001177478.2		c.1695G>A	p.Lys565Lys	synonymous	Exon 9 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.1869G>A	p.Lys623Lys	synonymous	Exon 10 of 11	ENSP00000362272.2	Q7Z353-1
	HDX	ENST00000297977.9	TSL:1	c.1869G>A	p.Lys623Lys	synonymous	Exon 9 of 10	ENSP00000297977.5	Q7Z353-1
	HDX	ENST00000851225.1		c.1869G>A	p.Lys623Lys	synonymous	Exon 10 of 11	ENSP00000521284.1

Frequencies

GnomAD3 genomes AF: 0.00366 AC: 409 AN: 111679 Hom.: 9 Cov.: 23

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

GnomAD2 exomes AF: 0.00627 AC: 1136 AN: 181312 AF XY: 0.00401

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 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.: 31 Cov.: 25 AF XY: 0.00168 AC XY: 578 AN XY: 344569

African (AFR) AF: 0.000923 AC: 24 AN: 26005

American (AMR) AF: 0.0371 AC: 1295 AN: 34902

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19228

East Asian (EAS) AF: 0.0171 AC: 515 AN: 30059

South Asian (SAS) AF: 0.0000748 AC: 4 AN: 53490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40435

Middle Eastern (MID) AF: 0.000245 AC: 1 AN: 4083

European-Non Finnish (NFE) AF: 0.0000328 AC: 27 AN: 824177

Other (OTH) AF: 0.00216 AC: 98 AN: 45396

GnomAD4 genome AF: 0.00365 AC: 408 AN: 111731 Hom.: 9 Cov.: 23 AF XY: 0.00407 AC XY: 138 AN XY: 33947

African (AFR) AF: 0.00117 AC: 36 AN: 30781

American (AMR) AF: 0.0285 AC: 299 AN: 10496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2634

East Asian (EAS) AF: 0.0161 AC: 57 AN: 3533

South Asian (SAS) AF: 0.00 AC: 0 AN: 2712

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6005

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

European-Non Finnish (NFE) AF: 0.000169 AC: 9 AN: 53139

Other (OTH) AF: 0.00458 AC: 7 AN: 1529

Alfa AF: 0.00217 Hom.: 15

Bravo AF: 0.00636

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
CADD	Benign	6.2
DANN	Benign	0.61
PhyloP100		0.22
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: rs143487849; hg19: chrX-83581264; COSMIC: COSV52977257;