Variant 12-53945268-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.11

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1285351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 linkuse as main transcript	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 linkuse as main transcript	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.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.680

AC XY:

494285

AN XY:

726526

show subpopulations

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.:

AF XY:

0.586

AC XY:

43521

AN XY:

74296

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Ectodermal dysplasia 9, hair/nail type

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over