Variant X-84322014-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001177479.2(HDX):c.1948G>A(p.Ala650Thr) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000389 in 1,029,304 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000039 ( 0 hom. 0 hem. )

Consequence

HDX
NM_001177479.2 missense, splice_region

Scores

Splicing: ADA: 0.9633

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.69

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HDX	NM_001177479.2 linkuse as main transcript	c.1948G>A	p.Ala650Thr	missense_variant, splice_region_variant	11/11	ENST00000373177.3	NP_001170950.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HDX	ENST00000373177.3 linkuse as main transcript	c.1948G>A	p.Ala650Thr	missense_variant, splice_region_variant	11/11	1	NM_001177479.2	ENSP00000362272	P1	Q7Z353-1
HDX	ENST00000297977.9 linkuse as main transcript	c.1948G>A	p.Ala650Thr	missense_variant, splice_region_variant	10/10	1		ENSP00000297977	P1	Q7Z353-1
HDX	ENST00000506585.6 linkuse as main transcript	c.1774G>A	p.Ala592Thr	missense_variant, splice_region_variant	10/10	2		ENSP00000423670		Q7Z353-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000389

AC:

AN:

1029304

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

310588

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000351

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000250

Gnomad4 OTH exome

AF:

0.0000232

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

Apr 29, 2024

The c.1948G>A (p.A650T) alteration is located in exon 11 (coding exon 9) of the HDX gene. This alteration results from a G to A substitution at nucleotide position 1948, causing the alanine (A) at amino acid position 650 to be replaced by a threonine (T). 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

0.10

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

T;.;T

FATHMM_MKL

Uncertain

0.85

LIST_S2

Uncertain

0.88

.;D;D

M_CAP

Pathogenic

0.41

MetaRNN

Benign

0.40

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;.;L

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.54

N;.;.

REVEL

Benign

0.16

Sift

Benign

0.15

T;.;.

Sift4G

Benign

0.32

T;T;T

Polyphen

0.97

D;.;D

Vest4

0.31

MutPred

0.10

Gain of methylation at K645 (P = 0.0692);.;Gain of methylation at K645 (P = 0.0692);

MVP

0.42

MPC

0.13

ClinPred

0.74

GERP RS

5.5

Varity_R

0.069

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.96

dbscSNV1_RF

Benign

0.70

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.32

Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over