7-27165154-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152739.4(HOXA9):​c.304G>A​(p.Ala102Thr) 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. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A102P) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

HOXA9
NM_152739.4 missense

Scores

6
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.59
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.23187795).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
HOXA9NM_152739.4 linkc.304G>A p.Ala102Thr missense_variant Exon 1 of 2 ENST00000343483.7 NP_689952.1 P31269
HOXA10-HOXA9NR_037940.1 linkn.617-187G>A intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HOXA9ENST00000343483.7 linkc.304G>A p.Ala102Thr missense_variant Exon 1 of 2 1 NM_152739.4 ENSP00000343619.6 P31269
ENSG00000257184ENST00000470747.4 linkc.11-187G>A intron_variant Intron 1 of 2 3 ENSP00000421799.3 D6RAR5

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1443290
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
716476
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Benign
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.14
T;.
Eigen
Benign
-0.073
Eigen_PC
Benign
0.088
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.69
T;T
M_CAP
Uncertain
0.095
D
MetaRNN
Benign
0.23
T;T
MetaSVM
Uncertain
0.27
D
MutationAssessor
Benign
1.8
L;.
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
0.18
N;N
REVEL
Benign
0.27
Sift
Benign
0.57
T;T
Sift4G
Benign
0.54
T;T
Polyphen
0.025
B;.
Vest4
0.36
MutPred
0.43
Gain of glycosylation at A102 (P = 0.0179);Gain of glycosylation at A102 (P = 0.0179);
MVP
0.79
MPC
0.53
ClinPred
0.35
T
GERP RS
5.4
Varity_R
0.11
gMVP
0.20

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-27204773; API