7-27156361-T-C

Position:

• chr7-27156361-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006896.4(HOXA7):​c.185A>G​(p.Tyr62Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: HOXA7 NM_006896.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.98

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.796

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA7	NM_006896.4	c.185A>G	p.Tyr62Cys	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.185A>G	p.Tyr62Cys	missense_variant	1/2	1	NM_006896.4	ENSP00000242159	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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

Nov 17, 2022

The c.185A>G (p.Y62C) alteration is located in exon 1 (coding exon 1) of the HOXA7 gene. This alteration results from a A to G substitution at nucleotide position 185, causing the tyrosine (Y) at amino acid position 62 to be replaced by a cysteine (C). 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	0.10
BayesDel_addAF	Uncertain	0.029	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.58	D
Eigen	Uncertain	0.62
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.015	T
MetaRNN	Pathogenic	0.80	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.1	M
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.14
Sift	Benign	0.088	T
Sift4G	Benign	0.092	T
Polyphen		1.0	D
Vest4		0.84
MutPred		0.34		Gain of catalytic residue at L61 (P = 0.2258);
MVP		0.75
MPC		1.3
ClinPred		0.95	D
GERP RS		5.6
Varity_R		0.27
gMVP		0.75

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: chr7-27195980;