rs1938563562

Variant summary

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

The NM_017410.3(HOXC13):​c.127G>A​(p.Gly43Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000076 in 1,316,280 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

HOXC13
NM_017410.3 missense

Scores

2
8
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.69
Variant links:
Genes affected
HOXC13 (HGNC:5125): (homeobox C13) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, which are located on different chromosomes and consist of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXC genes located in a cluster on chromosome 12. The product of this gene may play a role in the development of hair, nail, and filiform papilla. [provided by RefSeq, Jul 2008]
HOXC13-AS (HGNC:43753): (HOXC13 antisense RNA)

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ACMG classification

Classification made for transcript

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 rank MANE Protein UniProt
HOXC13NM_017410.3 linkc.127G>A p.Gly43Arg missense_variant Exon 1 of 2 ENST00000243056.5 NP_059106.2 P31276
HOXC13-ASNR_047507.1 linkn.173+438C>T intron_variant Intron 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
HOXC13ENST00000243056.5 linkc.127G>A p.Gly43Arg missense_variant Exon 1 of 2 1 NM_017410.3 ENSP00000243056.3 P31276
HOXC13-ASENST00000512916.2 linkn.173+438C>T intron_variant Intron 1 of 2 3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.60e-7
AC:
1
AN:
1316280
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
646888
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:
9.52e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Uncertain
0.10
D
BayesDel_noAF
Benign
-0.090
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.052
T
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.24
FATHMM_MKL
Benign
0.68
D
LIST_S2
Benign
0.64
T
M_CAP
Pathogenic
0.92
D
MetaRNN
Uncertain
0.70
D
MetaSVM
Uncertain
0.28
D
MutationAssessor
Benign
0.0
N
PrimateAI
Pathogenic
0.91
D
PROVEAN
Benign
-0.56
N
REVEL
Uncertain
0.39
Sift
Uncertain
0.0070
D
Sift4G
Benign
0.091
T
Polyphen
0.99
D
Vest4
0.47
MutPred
0.37
Gain of catalytic residue at S47 (P = 0);
MVP
0.91
MPC
1.9
ClinPred
0.81
D
GERP RS
3.0
Varity_R
0.15
gMVP
0.41

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: chr12-54332817; API