Variant chr7-27165154-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_152739.4(HOXA9):c.304G>C(p.Ala102Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00483 in 1,595,632 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0041 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 24 hom. )

Consequence

HOXA9
NM_152739.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

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]

HOXA9 links:

HOXA10-HOXA9 (HGNC:):

HOXA10-HOXA9 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008946419).

BS2

High AC in GnomAd4 at 623 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXA9	NM_152739.4 linkuse as main transcript	c.304G>C	p.Ala102Pro	missense_variant	1/2	ENST00000343483.7
HOXA10-HOXA9	NR_037940.1 linkuse as main transcript	n.617-187G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXA9	ENST00000343483.7 linkuse as main transcript	c.304G>C	p.Ala102Pro	missense_variant	1/2	1	NM_152739.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00410

AC:

624

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00739

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.00198

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00605

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00365

AC:

805

AN:

220380

Hom.:

AF XY:

0.00358

AC XY:

436

AN XY:

121886

show subpopulations

Gnomad AFR exome

AF:

0.000700

Gnomad AMR exome

AF:

0.00471

Gnomad ASJ exome

AF:

0.00105

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00160

Gnomad FIN exome

AF:

0.00235

Gnomad NFE exome

AF:

0.00530

Gnomad OTH exome

AF:

0.00564

GnomAD4 exome

AF:

0.00491

AC:

7091

AN:

1443280

Hom.:

Cov.:

AF XY:

0.00483

AC XY:

3457

AN XY:

716470

show subpopulations

Gnomad4 AFR exome

AF:

0.000579

Gnomad4 AMR exome

AF:

0.00487

Gnomad4 ASJ exome

AF:

0.000871

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00186

Gnomad4 FIN exome

AF:

0.00208

Gnomad4 NFE exome

AF:

0.00564

Gnomad4 OTH exome

AF:

0.00544

GnomAD4 genome

AF:

0.00409

AC:

623

AN:

152352

Hom.:

Cov.:

AF XY:

0.00403

AC XY:

300

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00144

Gnomad4 AMR

AF:

0.00738

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.00198

Gnomad4 NFE

AF:

0.00604

Gnomad4 OTH

AF:

0.00473

Alfa

AF:

0.00389

Hom.:

Bravo

AF:

0.00426

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00122

AC:

ESP6500EA

AF:

0.00533

AC:

ExAC

AF:

0.00303

AC:

357

Asia WGS

AF:

0.00115

AC:

AN:

3476

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Hand-foot-genital syndrome

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Zaffran Lab, Genetics of Cardiac Diseases Laboratory, Marseille Medical Genetics

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.15

T;.

Eigen

Benign

-0.10

Eigen_PC

Benign

0.080

FATHMM_MKL

Benign

0.73

LIST_S2

Benign

0.65

T;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.0089

T;T

MetaSVM

Uncertain

0.054

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.30

N;N

REVEL

Benign

0.28

Sift

Benign

0.25

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.0060

B;.

Vest4

0.50

MVP

0.83

MPC

0.56

ClinPred

0.023

GERP RS

5.4

Varity_R

0.31

gMVP

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over