7-27199239-G-A

Position:

• chr7-27199239-G-A

Variant summary

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

The NM_000522.5(HOXA13):​c.839C>T​(p.Ala280Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HOXA13 NM_000522.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.76

Genes affected

HOXA13 (HGNC:5102): (homeobox A13) 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. Expansion of a polyalanine tract in the encoded protein can cause hand-foot-uterus syndrome, also known as hand-foot-genital syndrome. [provided by RefSeq, Jul 2008]

HOTTIP (HGNC:):

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
HOXA13	NM_000522.5	c.839C>T	p.Ala280Val	missense_variant	1/2	ENST00000649031.1	NP_000513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXA13	ENST00000649031.1	c.839C>T	p.Ala280Val	missense_variant	1/2		NM_000522.5	ENSP00000497112.1
HOTTIP	ENST00000421733.1	n.167+498G>A		intron_variant		5
HOTTIP	ENST00000605136.6	n.-6G>A		upstream_gene_variant		2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hand-foot-genital syndrome;C1867801:Guttmacher syndrome Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Pathogenic	33
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.29	T;T
Eigen	Pathogenic	0.71
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	.;D
M_CAP	Benign	0.064	D
MetaRNN	Uncertain	0.49	T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.7	M;M
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-2.3	.;N
REVEL	Uncertain	0.29
Sift	Uncertain	0.0030	.;D
Sift4G	Benign	0.16	.;T
Polyphen		0.98	D;D
Vest4		0.48
MutPred		0.36		Loss of disorder (P = 0.1006);Loss of disorder (P = 0.1006);
MVP		0.76
ClinPred		0.99	D
GERP RS		4.9
Varity_R		0.48
gMVP		0.62

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: chr7-27238858;