12-53939166-C-T

Variant names:

• chr12-53939166-C-T
• rs904926695
• NM_017410.3:c.260C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_017410.3(HOXC13):​c.260C>T​(p.Ala87Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000148 in 1,485,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (0 hom.)
• Consequence: HOXC13 NM_017410.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 0.614
• Publications: 0 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-AS (HGNC:43753): (HOXC13 antisense RNA)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.12060231).

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>T	p.Ala87Val	missense	Exon 1 of 2	NP_059106.2
	HOXC13-AS	NR_047507.1		n.173+305G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HOXC13	ENST00000243056.5	TSL:1 MANE Select	c.260C>T	p.Ala87Val	missense	Exon 1 of 2	ENSP00000243056.3	P31276
	HOXC13-AS	ENST00000512916.3	TSL:3	n.222+305G>A		intron	N/A
	HOXC13-AS	ENST00000810609.1		n.181+305G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152042 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000393

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000739 AC: 6 AN: 81232 AF XY: 0.0000431

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000426

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000120 AC: 16 AN: 1333558 Hom.: 0 Cov.: 33 AF XY: 0.00000913 AC XY: 6 AN XY: 657118

African (AFR) AF: 0.00 AC: 0 AN: 26508

American (AMR) AF: 0.000273 AC: 7 AN: 25624

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22438

East Asian (EAS) AF: 0.00 AC: 0 AN: 32020

South Asian (SAS) AF: 0.00 AC: 0 AN: 72188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4332

European-Non Finnish (NFE) AF: 0.00000849 AC: 9 AN: 1060464

Other (OTH) AF: 0.00 AC: 0 AN: 55380

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152042 Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3 AN XY: 74256

African (AFR) AF: 0.00 AC: 0 AN: 41420

American (AMR) AF: 0.000393 AC: 6 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67960

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000436 Hom.: 0

Bravo AF: 0.0000416

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.083	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.57	T
M_CAP	Uncertain	0.26	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	2.0	M
PhyloP100		0.61
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.045
Sift	Benign	0.32	T
Sift4G	Benign	0.21	T
Polyphen		0.24	B
Vest4		0.050
MutPred		0.29		Gain of catalytic residue at A87 (P = 5e-04)
MVP		0.55
MPC		0.87
ClinPred		0.084	T
GERP RS		2.8
PromoterAI		-0.029	Neutral
Varity_R		0.12
gMVP		0.27
Mutation Taster		=88/12	polymorphism

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: rs904926695; hg19: chr12-54332950;