dbSNP rs1439072605: HOXA4:p.Gly125Val (chr7-27130360-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_002141.5(HOXA4):c.374G>T(p.Gly125Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G125D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 34)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HOXA4
NM_002141.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.870

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:

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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=0.23925707).

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.374G>T	p.Gly125Val	missense	Exon 1 of 2	NP_002132.3
HOXA3	NM_153631.3	MANE Select	c.-389-3290G>T		intron	N/A	NP_705895.1	O43365
HOXA3	NM_001384335.1		c.-505-3290G>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.374G>T	p.Gly125Val	missense	Exon 1 of 2	ENSP00000353151.5	Q00056
HOXA4	ENST00000610970.1	TSL:1	c.374G>T	p.Gly125Val	missense	Exon 1 of 2	ENSP00000479166.1	Q00056
HOXA3	ENST00000612286.5	TSL:2 MANE Select	c.-389-3290G>T		intron	N/A	ENSP00000484411.1	O43365

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

987294

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

463244

African (AFR)

AF:

0.00

AC:

AN:

18848

American (AMR)

AF:

0.00

AC:

AN:

5426

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

9910

East Asian (EAS)

AF:

0.00

AC:

AN:

17612

South Asian (SAS)

AF:

0.00

AC:

AN:

18726

European-Finnish (FIN)

AF:

0.00

AC:

AN:

16962

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2402

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

860682

Other (OTH)

AF:

0.00

AC:

AN:

36726

GnomAD4 genome

Cov.:

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

0.094

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.055

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.52

M_CAP

Pathogenic

0.82

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.44

MutationAssessor

Benign

0.69

PhyloP100

0.87

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.0

REVEL

Benign

0.18

Sift

Benign

0.11

Sift4G

Benign

0.20

Polyphen

0.0080

Vest4

0.27

MutPred

0.34

Gain of sheet (P = 0.0266)

MVP

0.87

MPC

1.6

ClinPred

0.23

GERP RS

2.8

PromoterAI

-0.13

Neutral

(source)

Varity_R

0.063

gMVP

0.34

Mutation Taster

=97/3

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over