X-84469119-C-T

Position:

• chrX-84469119-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001177479.2(HDX):​c.604G>A​(p.Val202Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 22)
• Consequence: HDX NM_001177479.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.106756926).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDX	NM_001177479.2	c.604G>A	p.Val202Ile	missense_variant	4/11	ENST00000373177.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDX	ENST00000373177.3	c.604G>A	p.Val202Ile	missense_variant	4/11	1	NM_001177479.2	P1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 29, 2023

The c.604G>A (p.V202I) alteration is located in exon 4 (coding exon 2) of the HDX gene. This alteration results from a G to A substitution at nucleotide position 604, causing the valine (V) at amino acid position 202 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.97
DEOGEN2	Benign	0.080	T;.;T;.
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.79	.;T;T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.11	T;T;T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.8	L;.;L;.
MutationTaster	Benign	0.85	N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.66	N;.;.;N
REVEL	Benign	0.090
Sift	Benign	0.58	T;.;.;T
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.018	B;.;B;.
Vest4		0.11
MutPred		0.13		Loss of MoRF binding (P = 0.176);.;Loss of MoRF binding (P = 0.176);.;
MVP		0.38
MPC		0.099
ClinPred		0.053	T
GERP RS		3.0
Varity_R		0.050
gMVP		0.14

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-83724127;