Genetic Variant NM_152739.4:c.394A>G (chr7-27165064-T-C) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_152739.4(HOXA9):c.394A>G(p.Ile132Val) 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Consequence

HOXA9
NM_152739.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.06

Publications

0 publications found

Variant links:

Genes affected

HOXA9 (HGNC:5109): (homeobox A9) 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. This gene is highly similar to the abdominal-B (Abd-B) gene of Drosophila. A specific translocation event which causes a fusion between this gene and the NUP98 gene has been associated with myeloid leukemogenesis. Read-through transcription exists between this gene and the upstream homeobox A10 (HOXA10) gene.[provided by RefSeq, Mar 2011]

HOXA9 links:

HOXA10-HOXA9 (HGNC:51908):

HOXA10-HOXA9 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.27777672).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152739.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXA9	NM_152739.4	MANE Select	c.394A>G	p.Ile132Val	missense	Exon 1 of 2	NP_689952.1	P31269
	HOXA10-HOXA9	NM_001433944.1		c.11-97A>G		intron	N/A	NP_001420873.1	D6RAR5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXA9	ENST00000343483.7	TSL:1 MANE Select	c.394A>G	p.Ile132Val	missense	Exon 1 of 2	ENSP00000343619.6	P31269
HOXA10-HOXA9	ENST00000470747.5	TSL:3	c.11-97A>G		intron	N/A	ENSP00000421799.3
HOXA9	ENST00000465941.1	TSL:1	n.480-1223A>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

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

0.15

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.19

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.89

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.28

MetaSVM

Uncertain

0.25

MutationAssessor

Benign

1.6

PhyloP100

1.1

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.42

REVEL

Uncertain

0.33

Sift

Benign

0.40

Sift4G

Benign

0.41

Polyphen

0.39

Vest4

0.14

MutPred

0.54

Loss of catalytic residue at L137 (P = 0.0367)

MVP

0.89

MPC

1.1

ClinPred

0.64

GERP RS

5.7

PromoterAI

0.041

Neutral

(source)

Varity_R

0.12

gMVP

0.21

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

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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