rs398122913

Variant names:

• chr12-53939296-C-A
• rs398122913
• NM_017410.3:c.390C>A

Your query was ambiguous. Multiple possible variants found:

• chr12-53939296-C-A
• chr12-53939296-C-G
• chr12-53939296-C-T

Variant summary

Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_017410.3(HOXC13):​c.390C>A​(p.Tyr130*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HOXC13 NM_017410.3 stop_gained
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 0.627
• Publications: 2 publications found

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)

ACMG classification

Our verdict: Pathogenic. The variant received 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 12-53939296-C-A is Pathogenic according to our data. Variant chr12-53939296-C-A is described in ClinVar as Pathogenic. ClinVar VariationId is 39781.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXC13	NM_017410.3	c.390C>A	p.Tyr130*	stop_gained	Exon 1 of 2	ENST00000243056.5	NP_059106.2
HOXC13-AS	NR_047507.1	n.173+175G>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXC13	ENST00000243056.5	c.390C>A	p.Tyr130*	stop_gained	Exon 1 of 2	1	NM_017410.3	ENSP00000243056.3
HOXC13-AS	ENST00000512916.3	n.222+175G>T		intron_variant	Intron 1 of 2	3
HOXC13-AS	ENST00000810609.1	n.181+175G>T		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1422206 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 704310

African (AFR) AF: 0.00 AC: 0 AN: 32550

American (AMR) AF: 0.00 AC: 0 AN: 39248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25422

East Asian (EAS) AF: 0.00 AC: 0 AN: 37412

South Asian (SAS) AF: 0.00 AC: 0 AN: 81662

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48064

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5728

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1093276

Other (OTH) AF: 0.00 AC: 0 AN: 58844

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000608 Hom.: 0

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Ectodermal dysplasia 9, hair/nail type Pathogenic:1

Nov 02, 2012

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.59	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.80	D
PhyloP100		0.63
Vest4		0.88
GERP RS		2.7
PromoterAI		-0.048	Neutral
Mutation Taster		=1/199	disease causing (ClinVar)

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

Other links and lift over

dbSNP: rs398122913; hg19: chr12-54333080;