Variant X-84333786-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001177479.2(HDX):c.1797A>T(p.Glu599Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000118 in 848,523 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000012 ( 0 hom. 1 hem. )

Consequence

HDX
NM_001177479.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.103

Variant links:

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]

HDX links:

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ACMG classification

Classification made for transcript

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=0.121939).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HDX	NM_001177479.2 linkuse as main transcript	c.1797A>T	p.Glu599Asp	missense_variant	9/11	ENST00000373177.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HDX	ENST00000373177.3 linkuse as main transcript	c.1797A>T	p.Glu599Asp	missense_variant	9/11	1	NM_001177479.2	P1	Q7Z353-1
HDX	ENST00000297977.9 linkuse as main transcript	c.1797A>T	p.Glu599Asp	missense_variant	8/10	1		P1	Q7Z353-1
HDX	ENST00000506585.6 linkuse as main transcript	c.1623A>T	p.Glu541Asp	missense_variant	8/10	2			Q7Z353-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000661

AC:

AN:

151319

Hom.:

AF XY:

0.0000230

AC XY:

AN XY:

43541

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000442

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000118

AC:

AN:

848523

Hom.:

Cov.:

AF XY:

0.00000420

AC XY:

AN XY:

237973

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000317

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 02, 2024

The c.1797A>T (p.E599D) alteration is located in exon 9 (coding exon 7) of the HDX gene. This alteration results from a A to T substitution at nucleotide position 1797, causing the glutamic acid (E) at amino acid position 599 to be replaced by an aspartic acid (D). 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

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.85

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.069

T;.;T

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.73

.;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;.;L

MutationTaster

Benign

0.72

N;N;N

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.94

N;.;.

REVEL

Benign

0.093

Sift

Benign

0.22

T;.;.

Sift4G

Benign

0.24

T;T;T

Polyphen

0.0090

B;.;B

Vest4

0.22

MutPred

0.11

Loss of helix (P = 0.0558);.;Loss of helix (P = 0.0558);

MVP

0.13

MPC

0.11

ClinPred

0.079

GERP RS

-0.44

Varity_R

0.14

gMVP

0.092

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over