Variant 12-53939187-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_017410.3(HOXC13):c.281C>A(p.Thr94Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00334 in 1,522,010 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T94A) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0026 ( 3 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 16 hom. )

Consequence

HOXC13
NM_017410.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.02

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008624017).

BP6

Variant 12-53939187-C-A is Benign according to our data. Variant chr12-53939187-C-A is described in ClinVar as [Benign]. Clinvar id is 1588495.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXC13	NM_017410.3 linkuse as main transcript	c.281C>A	p.Thr94Lys	missense_variant	1/2	ENST00000243056.5
HOXC13-AS	NR_047507.1 linkuse as main transcript	n.173+284G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXC13	ENST00000243056.5 linkuse as main transcript	c.281C>A	p.Thr94Lys	missense_variant	1/2	1	NM_017410.3	P1
HOXC13-AS	ENST00000512916.2 linkuse as main transcript	n.173+284G>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00256

AC:

390

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000700

Gnomad AMI

AF:

0.00439

Gnomad AMR

AF:

0.00268

Gnomad ASJ

AF:

0.00979

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00744

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00318

Gnomad NFE

AF:

0.00351

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00392

AC:

461

AN:

117550

Hom.:

AF XY:

0.00438

AC XY:

285

AN XY:

65134

show subpopulations

Gnomad AFR exome

AF:

0.000812

Gnomad AMR exome

AF:

0.00199

Gnomad ASJ exome

AF:

0.0108

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00665

Gnomad FIN exome

AF:

0.000144

Gnomad NFE exome

AF:

0.00426

Gnomad OTH exome

AF:

0.00367

GnomAD4 exome

AF:

0.00342

AC:

4689

AN:

1369764

Hom.:

Cov.:

AF XY:

0.00353

AC XY:

2386

AN XY:

675528

show subpopulations

Gnomad4 AFR exome

AF:

0.000569

Gnomad4 AMR exome

AF:

0.00191

Gnomad4 ASJ exome

AF:

0.00967

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00589

Gnomad4 FIN exome

AF:

0.000110

Gnomad4 NFE exome

AF:

0.00335

Gnomad4 OTH exome

AF:

0.00518

GnomAD4 genome

AF:

0.00257

AC:

391

AN:

152246

Hom.:

Cov.:

AF XY:

0.00265

AC XY:

197

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.000698

Gnomad4 AMR

AF:

0.00268

Gnomad4 ASJ

AF:

0.00979

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00745

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.00353

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00403

Hom.:

Bravo

AF:

0.00244

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00259

AC:

ESP6500AA

AF:

0.000385

AC:

ESP6500EA

AF:

0.00280

AC:

ExAC

AF:

0.00162

AC:

138

Asia WGS

AF:

0.00260

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.41

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.40

Cadd

Uncertain

Dann

Benign

0.97

DEOGEN2

Benign

0.089

Eigen

Benign

0.00060

Eigen_PC

Benign

-0.0037

FATHMM_MKL

Benign

0.63

LIST_S2

Benign

0.86

MetaRNN

Benign

0.0086

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.94

PROVEAN

Benign

-1.0

REVEL

Benign

0.066

Sift

Uncertain

0.026

Sift4G

Benign

0.48

Polyphen

0.48

Vest4

0.27

MVP

0.81

MPC

1.1

ClinPred

0.027

GERP RS

2.2

Varity_R

0.15

gMVP

0.40

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