dbSNP rs777763154: HDX:p.Asp455Gly (chrX-84361554-T-C) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP3BS2

The NM_001177479.2(HDX):c.1364A>G(p.Asp455Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000416 in 1,200,935 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000089 ( 0 hom., 0 hem., cov: 23)

Exomes 𝑓: 0.0000037 ( 0 hom. 3 hem. )

Consequence

HDX
NM_001177479.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.84

Publications

1 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.764

BS2

High Hemizygotes in GnomAdExome4 at 3 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDX	NM_001177479.2	MANE Select	c.1364A>G	p.Asp455Gly	missense	Exon 6 of 11	NP_001170950.1	Q7Z353-1
HDX	NM_144657.5		c.1364A>G	p.Asp455Gly	missense	Exon 5 of 10	NP_653258.2
HDX	NM_001177478.2		c.1190A>G	p.Asp397Gly	missense	Exon 5 of 10	NP_001170949.1	Q7Z353-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HDX	ENST00000373177.3	TSL:1 MANE Select	c.1364A>G	p.Asp455Gly	missense	Exon 6 of 11	ENSP00000362272.2	Q7Z353-1
HDX	ENST00000297977.9	TSL:1	c.1364A>G	p.Asp455Gly	missense	Exon 5 of 10	ENSP00000297977.5	Q7Z353-1
HDX	ENST00000851225.1		c.1364A>G	p.Asp455Gly	missense	Exon 6 of 11	ENSP00000521284.1

Frequencies

GnomAD3 genomes

AF:

0.00000893

AC:

AN:

111988

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000278

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000336

AC:

AN:

178468

AF XY:

0.0000632

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000441

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000367

AC:

AN:

1088947

Hom.:

Cov.:

AF XY:

0.00000846

AC XY:

AN XY:

354687

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26221

American (AMR)

AF:

0.00

AC:

AN:

34923

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19266

East Asian (EAS)

AF:

0.000133

AC:

AN:

30082

South Asian (SAS)

AF:

0.00

AC:

AN:

53279

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4113

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

834939

Other (OTH)

AF:

0.00

AC:

AN:

45730

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.675

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000893

AC:

AN:

111988

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34150

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30816

American (AMR)

AF:

0.00

AC:

AN:

10461

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2645

East Asian (EAS)

AF:

0.000278

AC:

AN:

3593

South Asian (SAS)

AF:

0.00

AC:

AN:

2678

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6145

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

53222

Other (OTH)

AF:

0.00

AC:

AN:

1503

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000330

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Uncertain

0.069

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.85

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.24

MetaRNN

Pathogenic

0.76

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.8

PhyloP100

7.8

PrimateAI

Uncertain

0.75

PROVEAN

Pathogenic

-4.4

REVEL

Uncertain

0.53

Sift

Uncertain

0.0030

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.92

MutPred

0.25

Gain of MoRF binding (P = 0.0469)

MVP

0.80

MPC

0.66

ClinPred

0.68

GERP RS

5.2

Varity_R

0.85

gMVP

0.75

Mutation Taster

=82/18

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over