NM_002141.5:c.215C>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002141.5(HOXA4):c.215C>T(p.Ser72Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000487 in 1,335,404 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000047 ( 1 hom. )

Consequence

HOXA4
NM_002141.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.544

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19644052).

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.215C>T	p.Ser72Phe	missense	Exon 1 of 2	NP_002132.3
HOXA3	NM_153631.3	MANE Select	c.-389-3449C>T		intron	N/A	NP_705895.1	O43365
HOXA3	NM_001384335.1		c.-505-3449C>T		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.215C>T	p.Ser72Phe	missense	Exon 1 of 2	ENSP00000353151.5	Q00056
HOXA4	ENST00000610970.1	TSL:1	c.215C>T	p.Ser72Phe	missense	Exon 1 of 2	ENSP00000479166.1	Q00056
HOXA3	ENST00000612286.5	TSL:2 MANE Select	c.-389-3449C>T		intron	N/A	ENSP00000484411.1	O43365

Frequencies

GnomAD3 genomes

AF:

0.0000598

AC:

AN:

150410

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

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:

0.0000741

Gnomad OTH

AF:

0.000969

GnomAD2 exomes

AF:

0.0000532

AC:

AN:

37596

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000191

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000858

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000473

AC:

AN:

1184994

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

575626

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23278

American (AMR)

AF:

0.0000719

AC:

AN:

13906

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16326

East Asian (EAS)

AF:

0.00

AC:

AN:

25370

South Asian (SAS)

AF:

0.0000454

AC:

AN:

44032

European-Finnish (FIN)

AF:

0.0000265

AC:

AN:

37738

Middle Eastern (MID)

AF:

0.000303

AC:

AN:

3304

European-Non Finnish (NFE)

AF:

0.0000493

AC:

AN:

973560

Other (OTH)

AF:

0.0000632

AC:

AN:

47480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

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:

0.0000598

AC:

AN:

150410

Hom.:

Cov.:

AF XY:

0.0000545

AC XY:

AN XY:

73382

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41228

American (AMR)

AF:

0.000132

AC:

AN:

15132

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3450

East Asian (EAS)

AF:

0.00

AC:

AN:

5142

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9896

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000741

AC:

AN:

67438

Other (OTH)

AF:

0.000969

AC:

AN:

2064

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.000108

Hom.:

ExAC

AF:

0.0000442

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

0.28

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.037

Eigen

Benign

-0.23

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.48

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.34

PhyloP100

0.54

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.28

REVEL

Benign

0.065

Sift

Benign

0.12

Sift4G

Benign

0.073

Polyphen

0.32

Vest4

0.24

MVP

0.77

MPC

0.99

ClinPred

0.091

GERP RS

2.5

PromoterAI

-0.038

Neutral

(source)

Varity_R

0.16

gMVP

0.26

Mutation Taster

=88/12

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