X-84321944-T-A
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_001177479.2(HDX):c.2018A>T(p.Asp673Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000382 in 1,177,413 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 16 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000036 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.000038 ( 0 hom. 15 hem. )
Consequence
HDX
NM_001177479.2 missense
NM_001177479.2 missense
Scores
9
8
Clinical Significance
Conservation
PhyloP100: 3.75
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High Hemizygotes in GnomAdExome4 at 15 gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
HDX | NM_001177479.2 | c.2018A>T | p.Asp673Val | missense_variant | 11/11 | ENST00000373177.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HDX | ENST00000373177.3 | c.2018A>T | p.Asp673Val | missense_variant | 11/11 | 1 | NM_001177479.2 | P1 | |
HDX | ENST00000297977.9 | c.2018A>T | p.Asp673Val | missense_variant | 10/10 | 1 | P1 | ||
HDX | ENST00000506585.6 | c.1844A>T | p.Asp615Val | missense_variant | 10/10 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000360 AC: 4AN: 111046Hom.: 0 Cov.: 22 AF XY: 0.0000298 AC XY: 1AN XY: 33526
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GnomAD3 exomes AF: 0.0000229 AC: 4AN: 174470Hom.: 0 AF XY: 0.0000166 AC XY: 1AN XY: 60374
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GnomAD4 exome AF: 0.0000385 AC: 41AN: 1066315Hom.: 0 Cov.: 22 AF XY: 0.0000448 AC XY: 15AN XY: 335193
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GnomAD4 genome AF: 0.0000360 AC: 4AN: 111098Hom.: 0 Cov.: 22 AF XY: 0.0000298 AC XY: 1AN XY: 33588
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 14, 2023 | The c.2018A>T (p.D673V) alteration is located in exon 11 (coding exon 9) of the HDX gene. This alteration results from a A to T substitution at nucleotide position 2018, causing the aspartic acid (D) at amino acid position 673 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Uncertain
T;.;T
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
.;T;T
M_CAP
Uncertain
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
M;.;M
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;.;.
REVEL
Benign
Sift
Uncertain
D;.;.
Sift4G
Uncertain
T;T;T
Polyphen
D;.;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at