Variant 7-27156476-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_006896.4(HOXA7):c.70G>A(p.Ala24Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000609 in 1,609,840 control chromosomes in the GnomAD database, including 2 homozygotes. 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.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 36)

Exomes 𝑓: 0.000064 ( 2 hom. )

Consequence

HOXA7
NM_006896.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.00

Variant links:

Genes affected

HOXA7 (HGNC:5108): (homeobox A7) 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. For example, the encoded protein represses the transcription of differentiation-specific genes during keratinocyte proliferation, but this repression is then overcome by differentiation signals. This gene is highly similar to the antennapedia (Antp) gene of Drosophila. [provided by RefSeq, Jul 2008]

HOXA7 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=0.044141114).

BS2

High AC in GnomAdExome4 at 94 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA7	NM_006896.4 linkuse as main transcript	c.70G>A	p.Ala24Thr	missense_variant	1/2	ENST00000242159.5	NP_008827.2	P31268

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA7	ENST00000242159.5 linkuse as main transcript	c.70G>A	p.Ala24Thr	missense_variant	1/2	1	NM_006896.4	ENSP00000242159.3		P31268
HOXA7	ENST00000519842.1 linkuse as main transcript	c.70G>A	p.Ala24Thr	missense_variant	3/3	3		ENSP00000428563.1		E5RHM9

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000827

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000141

AC:

AN:

248024

Hom.:

AF XY:

0.000208

AC XY:

AN XY:

134608

show subpopulations

Gnomad AFR exome

AF:

0.0000638

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00109

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000645

AC:

AN:

1457462

Hom.:

Cov.:

AF XY:

0.0000966

AC XY:

AN XY:

724426

show subpopulations

Gnomad4 AFR exome

AF:

0.0000300

Gnomad4 AMR exome

AF:

0.0000225

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000966

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000116

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152378

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000828

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.000157

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 19, 2024

The c.70G>A (p.A24T) alteration is located in exon 1 (coding exon 1) of the HOXA7 gene. This alteration results from a G to A substitution at nucleotide position 70, causing the alanine (A) at amino acid position 24 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.069

T;.

Eigen

Benign

0.073

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.044

T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.5

L;.

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.55

N;N

REVEL

Benign

0.078

Sift

Benign

0.16

T;.

Sift4G

Benign

0.23

T;.

Polyphen

0.067

B;.

Vest4

0.56

MutPred

0.26

Gain of glycosylation at A24 (P = 0.1103);Gain of glycosylation at A24 (P = 0.1103);

MVP

0.74

MPC

0.38

ClinPred

0.038

GERP RS

5.2

Varity_R

0.11

gMVP

0.52

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