Genetic Variant NM_017410.3:c.127G>A (chr12-53939033-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 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

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.69

Publications

0 publications found

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 links:

HOXC13-AS (HGNC:43753): (HOXC13 antisense RNA)

HOXC13-AS links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017410.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXC13	NM_017410.3	MANE Select	c.127G>A	p.Gly43Arg	missense	Exon 1 of 2	NP_059106.2
	HOXC13-AS	NR_047507.1		n.173+438C>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXC13	ENST00000243056.5	TSL:1 MANE Select	c.127G>A	p.Gly43Arg	missense	Exon 1 of 2	ENSP00000243056.3	P31276
HOXC13-AS	ENST00000512916.3	TSL:3	n.222+438C>T		intron	N/A
HOXC13-AS	ENST00000810609.1		n.181+438C>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.60e-7

AC:

AN:

1316280

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

646888

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26470

American (AMR)

AF:

0.00

AC:

AN:

26376

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21538

East Asian (EAS)

AF:

0.00

AC:

AN:

30290

South Asian (SAS)

AF:

0.00

AC:

AN:

69926

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32496

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4318

European-Non Finnish (NFE)

AF:

9.52e-7

AC:

AN:

1050120

Other (OTH)

AF:

0.00

AC:

AN:

54746

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

Eigen

Uncertain

0.26

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.64

M_CAP

Pathogenic

0.92

MetaRNN

Uncertain

0.70

MetaSVM

Uncertain

0.28

MutationAssessor

Benign

0.0

PhyloP100

3.7

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.56

REVEL

Uncertain

0.39

Sift

Uncertain

0.0070

Sift4G

Benign

0.091

Polyphen

0.99

Vest4

0.47

MutPred

0.37

Gain of catalytic residue at S47 (P = 0)

MVP

0.91

MPC

1.9

ClinPred

0.81

GERP RS

3.0

PromoterAI

0.020

Neutral

(source)

Varity_R

0.15

gMVP

0.41

Mutation Taster

=91/9

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over