7-27154980-C-T

Position:

• chr7-27154980-C-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The ENST00000242159.5(HOXA7):​c.622G>A​(p.Ala208Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000089 in 1,461,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000089 (0 hom.)
• Consequence: HOXA7 ENST00000242159.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.390

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]

HOXA-AS3 (HGNC:43748): (HOXA cluster antisense RNA 3)

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.06322715).
• BS2: High AC in GnomAdExome4 at 13 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA7	NM_006896.4	c.622G>A	p.Ala208Thr	missense_variant	2/2	ENST00000242159.5	NP_008827.2
HOXA-AS3	NR_038832.1	n.2970C>T		non_coding_transcript_exon_variant	3/3
HOXA-AS3	NR_038831.1	n.3044C>T		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA7	ENST00000242159.5	c.622G>A	p.Ala208Thr	missense_variant	2/2	1	NM_006896.4	ENSP00000242159	P1
HOXA-AS3	ENST00000518947.6	n.3044C>T		non_coding_transcript_exon_variant	3/3	2
HOXA7	ENST00000523796.2	n.275G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000890 AC: 13 AN: 1461264 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 726908

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.0000166

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

Mar 07, 2024

The c.622G>A (p.A208T) alteration is located in exon 2 (coding exon 2) of the HOXA7 gene. This alteration results from a G to A substitution at nucleotide position 622, causing the alanine (A) at amino acid position 208 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	0.071
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	4.7
DANN	Benign	0.90
DEOGEN2	Benign	0.032	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.32	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.068	D
MetaRNN	Benign	0.063	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.69	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	0.44	N
REVEL	Benign	0.12
Sift	Benign	0.12	T
Sift4G	Benign	0.55	T
Polyphen		0.0	B
Vest4		0.13
MutPred		0.18		Gain of phosphorylation at A208 (P = 0.0051);
MVP		0.58
MPC		0.38
ClinPred		0.053	T
GERP RS		-3.1
Varity_R		0.042
gMVP		0.23

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: chr7-27194599;