7-27198224-T-C

Variant names:

• chr7-27198224-T-C
• NM_000522.5:c.1141A>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_000522.5(HOXA13):​c.1141A>G​(p.Ile381Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: HOXA13 NM_000522.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.35

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09765598).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA13	NM_000522.5	c.1141A>G	p.Ile381Val	missense_variant	Exon 2 of 2	ENST00000649031.1	NP_000513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA13	ENST00000649031.1	c.1141A>G	p.Ile381Val	missense_variant	Exon 2 of 2		NM_000522.5	ENSP00000497112.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	20
DANN	Benign	0.84
DEOGEN2	Benign	0.054	T;T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.15
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Benign	0.81	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.098	T;T
MetaSVM	Uncertain	-0.24	T
MutationAssessor	Benign	-0.68	N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	0.16	.;N
REVEL	Uncertain	0.39
Sift	Benign	1.0	.;T
Sift4G	Benign	1.0	.;T
Polyphen		0.040	B;B
Vest4		0.14
MutPred		0.22		Loss of loop (P = 0.0512);Loss of loop (P = 0.0512);
MVP		0.80
ClinPred		0.42	T
GERP RS		5.8
Varity_R		0.11
gMVP		0.63

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: chr7-27237843;