7-27156487-A-C

Position:

• chr7-27156487-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000242159.5(HOXA7):​c.59T>G​(p.Leu20Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 36)
• Consequence: HOXA7 ENST00000242159.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.35

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA7	NM_006896.4	c.59T>G	p.Leu20Arg	missense_variant	1/2	ENST00000242159.5	NP_008827.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA7	ENST00000242159.5	c.59T>G	p.Leu20Arg	missense_variant	1/2	1	NM_006896.4	ENSP00000242159	P1
HOXA7	ENST00000519842.1	c.59T>G	p.Leu20Arg	missense_variant	3/3	3		ENSP00000428563

Frequencies

GnomAD3 genomes Cov.: 36

GnomAD4 exome Cov.: 50

GnomAD4 genome Cov.: 36

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2023

The c.59T>G (p.L20R) 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 59, causing the leucine (L) at amino acid position 20 to be replaced by an arginine (R). 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	Pathogenic	0.60
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.20
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T;.
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.66
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.82	T;D
M_CAP	Uncertain	0.11	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Uncertain	0.27	D
MutationAssessor	Benign	1.6	L;.
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.7	N;D
REVEL	Uncertain	0.43
Sift	Uncertain	0.0040	D;.
Sift4G	Uncertain	0.045	D;.
Polyphen		0.99	D;.
Vest4		0.86
MutPred		0.50		Gain of disorder (P = 0.0179);Gain of disorder (P = 0.0179);
MVP		0.93
MPC		1.1
ClinPred		0.76	D
GERP RS		5.2
Varity_R		0.44
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-27196106;