Variant 7-27156461-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_006896.4(HOXA7):c.85T>G(p.Cys29Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,848 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 37)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

HOXA7
NM_006896.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.34

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.81

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA7	NM_006896.4 linkuse as main transcript	c.85T>G	p.Cys29Gly	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.85T>G	p.Cys29Gly	missense_variant	1/2	1	NM_006896.4	ENSP00000242159.3		P31268
HOXA7	ENST00000519842.1 linkuse as main transcript	c.85T>G	p.Cys29Gly	missense_variant	3/3	3		ENSP00000428563.1		E5RHM9

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000160

AC:

AN:

249694

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000983

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460848

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726584

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000165

AC:

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

Jun 12, 2023

The c.85T>G (p.C29G) alteration is located in exon 1 (coding exon 1) of the HOXA7 gene. This alteration results from a T to G substitution at nucleotide position 85, causing the cysteine (C) at amino acid position 29 to be replaced by a glycine (G). 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

Uncertain

0.47

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Pathogenic

0.25

CADD

Uncertain

DANN

Uncertain

0.97

DEOGEN2

Uncertain

0.65

D;.

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;T

M_CAP

Uncertain

0.098

MetaRNN

Pathogenic

0.81

D;D

MetaSVM

Uncertain

0.045

MutationAssessor

Uncertain

2.5

M;.

PrimateAI

Uncertain

0.68

PROVEAN

Pathogenic

-4.9

D;D

REVEL

Pathogenic

0.71

Sift

Uncertain

0.0050

D;.

Sift4G

Uncertain

0.0090

D;.

Polyphen

0.22

B;.

Vest4

0.87

MutPred

0.47

Gain of glycosylation at T27 (P = 0.028);Gain of glycosylation at T27 (P = 0.028);

MVP

0.88

MPC

0.97

ClinPred

0.72

GERP RS

5.2

Varity_R

0.70

gMVP

0.74

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