NM_153631.3:c.973C>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_153631.3(HOXA3):c.973C>A(p.Pro325Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,516,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000081 ( 0 hom. )

Consequence

HOXA3
NM_153631.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

Publications

0 publications found

Variant links:

Genes affected

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:

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:

ENSG00000293629 (HGNC:):

ENSG00000293629 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055302054).

BS2

High AC in GnomAd4 at 14 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153631.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXA3	NM_153631.3	MANE Select	c.973C>A	p.Pro325Thr	missense	Exon 6 of 6	NP_705895.1	O43365
HOXA3	NM_001384335.1		c.973C>A	p.Pro325Thr	missense	Exon 7 of 7	NP_001371264.1	O43365
HOXA3	NM_001384336.1		c.973C>A	p.Pro325Thr	missense	Exon 5 of 5	NP_001371265.1	O43365

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXA3	ENST00000612286.5	TSL:2 MANE Select	c.973C>A	p.Pro325Thr	missense	Exon 6 of 6	ENSP00000484411.1	O43365
HOXA3	ENST00000396352.8	TSL:1	c.973C>A	p.Pro325Thr	missense	Exon 3 of 3	ENSP00000379640.3	O43365
HOXA3	ENST00000317201.7	TSL:5	c.973C>A	p.Pro325Thr	missense	Exon 5 of 5	ENSP00000324884.2	O43365

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000518

AC:

AN:

154496

AF XY:

0.0000478

show subpopulations

Gnomad AFR exome

AF:

0.000681

Gnomad AMR exome

AF:

0.00

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:

0.00000806

AC:

AN:

1364770

Hom.:

Cov.:

AF XY:

0.00000598

AC XY:

AN XY:

668858

show subpopulations

African (AFR)

AF:

0.000328

AC:

AN:

30460

American (AMR)

AF:

0.00

AC:

AN:

30698

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20042

East Asian (EAS)

AF:

0.00

AC:

AN:

38632

South Asian (SAS)

AF:

0.00

AC:

AN:

72250

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46734

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5262

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1064752

Other (OTH)

AF:

0.0000179

AC:

AN:

55940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

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:

0.0000920

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.000338

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

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:

0.0000712

Hom.:

Bravo

AF:

0.000151

ExAC

AF:

0.0000523

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

Benign

0.067

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.19

Eigen

Benign

0.026

Eigen_PC

Benign

0.21

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.85

M_CAP

Benign

0.072

MetaRNN

Benign

0.055

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

1.9

PhyloP100

3.4

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-2.1

REVEL

Uncertain

0.33

Sift

Benign

0.19

Sift4G

Benign

0.24

Polyphen

0.067

Vest4

0.15

MutPred

0.18

Gain of helix (P = 0.0078)

MVP

0.56

MPC

0.60

ClinPred

0.077

GERP RS

5.7

Varity_R

0.15

gMVP

0.38

Mutation Taster

=81/19

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