Genetic Variant NM_017410.3:c.260C>A (chr12-53939166-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017410.3(HOXC13):c.260C>A(p.Ala87Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A87V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HOXC13
NM_017410.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.614

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24865773).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017410.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXC13	NM_017410.3	MANE Select	c.260C>A	p.Ala87Asp	missense	Exon 1 of 2	NP_059106.2
	HOXC13-AS	NR_047507.1		n.173+305G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXC13	ENST00000243056.5	TSL:1 MANE Select	c.260C>A	p.Ala87Asp	missense	Exon 1 of 2	ENSP00000243056.3	P31276
HOXC13-AS	ENST00000512916.3	TSL:3	n.222+305G>T		intron	N/A
HOXC13-AS	ENST00000810609.1		n.181+305G>T		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1333558

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

657118

African (AFR)

AF:

0.00

AC:

AN:

26508

American (AMR)

AF:

0.00

AC:

AN:

25624

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22438

East Asian (EAS)

AF:

0.00

AC:

AN:

32020

South Asian (SAS)

AF:

0.00

AC:

AN:

72188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4332

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1060464

Other (OTH)

AF:

0.00

AC:

AN:

55380

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.094

Eigen

Benign

0.027

Eigen_PC

Benign

0.052

FATHMM_MKL

Benign

0.37

LIST_S2

Benign

0.47

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.96

MutationAssessor

Benign

2.0

PhyloP100

0.61

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.5

REVEL

Benign

0.12

Sift

Benign

0.056

Sift4G

Benign

0.28

Polyphen

0.60

Vest4

0.16

MutPred

0.26

Gain of catalytic residue at L85 (P = 0.0077)

MVP

0.67

MPC

1.3

ClinPred

0.67

GERP RS

2.8

PromoterAI

0.012

Neutral

(source)

Varity_R

0.37

gMVP

0.45

Mutation Taster

=78/22

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over