NM_002141.5:c.524G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_002141.5(HOXA4):c.524G>A(p.Cys175Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00013 in 1,534,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00076 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

HOXA4
NM_002141.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.905

Publications

1 publications found

Variant links:

Genes affected

HOXA4 (HGNC:5105): (homeobox A4) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. [provided by RefSeq, Jul 2008]

HOXA4 links:

HOXA3 (HGNC:5104): (homeobox A3) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

HOXA3 links:

ENSG00000273433 (HGNC:):

ENSG00000273433 links:

HOXA-AS3 (HGNC:43748): (HOXA cluster antisense RNA 3)

HOXA-AS3 links:

HOXA-AS2 (HGNC:43745): (HOXA cluster antisense RNA 2) This gene produces a long non-coding RNA that promotes cell proliferation. This transcript may interact with enhancer of zeste homolog 2 Polycomb repressive complex to repress gene expression. [provided by RefSeq, Dec 2017]

HOXA-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026495427).

BP6

Variant 7-27130210-C-T is Benign according to our data. Variant chr7-27130210-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3053757.Status of the report is no_assertion_criteria_provided, 0 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002141.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXA4	NM_002141.5	MANE Select	c.524G>A	p.Cys175Tyr	missense	Exon 1 of 2	NP_002132.3
HOXA3	NM_153631.3	MANE Select	c.-389-3140G>A		intron	N/A	NP_705895.1	O43365
HOXA3	NM_001384335.1		c.-505-3140G>A		intron	N/A	NP_001371264.1	O43365

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXA4	ENST00000360046.10	TSL:1 MANE Select	c.524G>A	p.Cys175Tyr	missense	Exon 1 of 2	ENSP00000353151.5	Q00056
HOXA4	ENST00000610970.1	TSL:1	c.524G>A	p.Cys175Tyr	missense	Exon 1 of 2	ENSP00000479166.1	Q00056
HOXA3	ENST00000612286.5	TSL:2 MANE Select	c.-389-3140G>A		intron	N/A	ENSP00000484411.1	O43365

Frequencies

GnomAD3 genomes

AF:

0.000759

AC:

115

AN:

151504

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00259

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000395

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.000157

AC:

AN:

139842

AF XY:

0.0000750

show subpopulations

Gnomad AFR exome

AF:

0.00329

Gnomad AMR exome

AF:

0.000168

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000607

AC:

AN:

1383110

Hom.:

Cov.:

AF XY:

0.0000466

AC XY:

AN XY:

686592

show subpopulations

African (AFR)

AF:

0.00243

AC:

AN:

29622

American (AMR)

AF:

0.000215

AC:

AN:

37242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24082

East Asian (EAS)

AF:

0.00

AC:

AN:

33786

South Asian (SAS)

AF:

0.00

AC:

AN:

79818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37394

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5574

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078500

Other (OTH)

AF:

0.0000701

AC:

AN:

57092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.000758

AC:

115

AN:

151616

Hom.:

Cov.:

AF XY:

0.000702

AC XY:

AN XY:

74108

show subpopulations

African (AFR)

AF:

0.00258

AC:

107

AN:

41492

American (AMR)

AF:

0.000394

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3458

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67854

Other (OTH)

AF:

0.000475

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.522

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:

0.000783

Hom.:

Bravo

AF:

0.000910

ESP6500AA

AF:

0.00178

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000175

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

HOXA4-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.77

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.39

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.33

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.50

MetaRNN

Benign

0.026

MetaSVM

Uncertain

0.18

MutationAssessor

Uncertain

2.4

PhyloP100

0.91

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.36

Sift

Benign

0.048

Sift4G

Benign

0.068

Polyphen

0.95

Vest4

0.53

MVP

0.93

MPC

1.2

ClinPred

0.055

GERP RS

4.2

PromoterAI

0.029

Neutral

(source)

Varity_R

0.25

gMVP

0.73

Mutation Taster

=87/13

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