rs4759058

Variant names:

• chr12-53945268-C-A
• rs4759058
• NM_017410.3:c.*12C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017410.3(HOXC13):​c.*12C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.678 in 1,612,576 control chromosomes in the GnomAD database, including 381,326 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.58 (28535 hom., cov: 31)
  • Exomes 𝑓: 0.69 (352791 hom.)
• Consequence: HOXC13 NM_017410.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.11
• Publications: 20 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 Gene-Disease associations (from GenCC):

• ectodermal dysplasia 9, hair/nail type

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• pure hair and nail ectodermal dysplasia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 12-53945268-C-A is Benign according to our data. Variant chr12-53945268-C-A is described in ClinVar as Benign. ClinVar VariationId is 1285351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXC13	NM_017410.3	c.*12C>A		3_prime_UTR_variant	Exon 2 of 2	ENST00000243056.5	NP_059106.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXC13	ENST00000243056.5	c.*12C>A		3_prime_UTR_variant	Exon 2 of 2	1	NM_017410.3	ENSP00000243056.3

Frequencies

GnomAD3 genomes AF: 0.584 AC: 88735 AN: 151914 Hom.: 28534 Cov.: 31

Gnomad AFR AF: 0.299

Gnomad AMI AF: 0.691

Gnomad AMR AF: 0.719

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.795

Gnomad SAS AF: 0.440

Gnomad FIN AF: 0.691

Gnomad MID AF: 0.548

Gnomad NFE AF: 0.703

Gnomad OTH AF: 0.603

GnomAD2 exomes AF: 0.651 AC: 163371 AN: 250986 AF XY: 0.645

Gnomad AFR exome AF: 0.288

Gnomad AMR exome AF: 0.784

Gnomad ASJ exome AF: 0.559

Gnomad EAS exome AF: 0.787

Gnomad FIN exome AF: 0.695

Gnomad NFE exome AF: 0.698

Gnomad OTH exome AF: 0.664

GnomAD4 exome AF: 0.687 AC: 1003894 AN: 1460542 Hom.: 352791 Cov.: 46 AF XY: 0.680 AC XY: 494285 AN XY: 726526

African (AFR) AF: 0.286 AC: 9555 AN: 33428

American (AMR) AF: 0.775 AC: 34615 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 14788 AN: 26124

East Asian (EAS) AF: 0.821 AC: 32583 AN: 39684

South Asian (SAS) AF: 0.443 AC: 38236 AN: 86240

European-Finnish (FIN) AF: 0.688 AC: 36673 AN: 53332

Middle Eastern (MID) AF: 0.502 AC: 2889 AN: 5758

European-Non Finnish (NFE) AF: 0.716 AC: 795413 AN: 1110948

Other (OTH) AF: 0.649 AC: 39142 AN: 60344

GnomAD4 genome AF: 0.584 AC: 88736 AN: 152034 Hom.: 28535 Cov.: 31 AF XY: 0.586 AC XY: 43521 AN XY: 74296

African (AFR) AF: 0.299 AC: 12377 AN: 41456

American (AMR) AF: 0.719 AC: 10993 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1981 AN: 3468

East Asian (EAS) AF: 0.794 AC: 4112 AN: 5176

South Asian (SAS) AF: 0.441 AC: 2124 AN: 4818

European-Finnish (FIN) AF: 0.691 AC: 7296 AN: 10554

Middle Eastern (MID) AF: 0.534 AC: 156 AN: 292

European-Non Finnish (NFE) AF: 0.703 AC: 47805 AN: 67960

Other (OTH) AF: 0.597 AC: 1262 AN: 2114

Alfa AF: 0.660 Hom.: 58595

Bravo AF: 0.581

Asia WGS AF: 0.540 AC: 1879 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Ectodermal dysplasia 9, hair/nail type Benign:1

Aug 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.0
DANN	Benign	0.68
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs4759058; hg19: chr12-54339052;