Variant 7-27198313-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_000522.5(HOXA13):c.1052A>G(p.Lys351Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

HOXA13
NM_000522.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

Variant links:

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]

HOXA13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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, 0.814

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXA13	NM_000522.5 link	c.1052A>G	p.Lys351Arg	missense_variant	Exon 2 of 2	ENST00000649031.1	NP_000513.2	P31271Q6DI00

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXA13	ENST00000649031.1 link	c.1052A>G	p.Lys351Arg	missense_variant	Exon 2 of 2		NM_000522.5	ENSP00000497112.1		P31271

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727248

show subpopulations

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jul 31, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1052A>G (p.K351R) alteration is located in exon 2 (coding exon 2) of the HOXA13 gene. This alteration results from a A to G substitution at nucleotide position 1052, causing the lysine (K) at amino acid position 351 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

Uncertain

0.55

BayesDel_addAF

Pathogenic

0.28

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.76

D;D

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.91

.;D

M_CAP

Uncertain

0.18

MetaRNN

Pathogenic

0.81

D;D

MetaSVM

Uncertain

0.71

MutationAssessor

Benign

-0.17

N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-2.5

.;D

REVEL

Pathogenic

0.73

Sift

Benign

0.041

.;D

Sift4G

Benign

0.28

.;T

Polyphen

0.77

P;P

Vest4

0.68

MutPred

0.51

Loss of methylation at K351 (P = 0.0052);Loss of methylation at K351 (P = 0.0052);

MVP

0.92

ClinPred

0.97

GERP RS

5.6

Varity_R

0.54

gMVP

0.65

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over