rs4759058

chr12-53945268-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate 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, single submitter B:1
• Conservation: PhyloP100: 1.11

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]

ACMG classification

Verdict is Benign. Variant got -14 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 id is 1285351.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr12-53945268-C-A is described in Lovd as [Benign].
• 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/exons	MANE	UniProt
HOXC13	NM_017410.3	c.*12C>A		3_prime_UTR_variant	2/2	ENST00000243056.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXC13	ENST00000243056.5	c.*12C>A		3_prime_UTR_variant	2/2	1	NM_017410.3	P1

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

GnomAD3 exomes AF: 0.651 AC: 163371 AN: 250986 Hom.: 55897 AF XY: 0.645 AC XY: 87538 AN XY: 135720

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 SAS exome AF: 0.433

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

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.775

Gnomad4 ASJ exome AF: 0.566

Gnomad4 EAS exome AF: 0.821

Gnomad4 SAS exome AF: 0.443

Gnomad4 FIN exome AF: 0.688

Gnomad4 NFE exome AF: 0.716

Gnomad4 OTH exome AF: 0.649

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

Gnomad4 AFR AF: 0.299

Gnomad4 AMR AF: 0.719

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.794

Gnomad4 SAS AF: 0.441

Gnomad4 FIN AF: 0.691

Gnomad4 NFE AF: 0.703

Gnomad4 OTH AF: 0.597

Alfa AF: 0.667 Hom.: 47173

Bravo AF: 0.581

Asia WGS AF: 0.540 AC: 1879 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Ectodermal dysplasia 9, hair/nail type Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	9.0
Dann	Benign	0.68

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

LitVar

Other links and lift over

dbSNP: rs4759058; hg19: chr12-54339052;