NM_017410.3:c.272C>T

Variant names:

• chr12-53939178-C-T
• rs1187256678
• NM_017410.3:c.272C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017410.3(HOXC13):​c.272C>T​(p.Ala91Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000658 in 152,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: HOXC13 NM_017410.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.26
• 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: 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=0.2436614).

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.272C>T	p.Ala91Val	missense	Exon 1 of 2	NP_059106.2
	HOXC13-AS	NR_047507.1		n.173+293G>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.272C>T	p.Ala91Val	missense	Exon 1 of 2	ENSP00000243056.3	P31276
	HOXC13-AS	ENST00000512916.3	TSL:3	n.222+293G>A		intron	N/A
	HOXC13-AS	ENST00000810609.1		n.181+293G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1355870 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 668684

African (AFR) AF: 0.00 AC: 0 AN: 28322

American (AMR) AF: 0.00 AC: 0 AN: 30460

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23626

East Asian (EAS) AF: 0.00 AC: 0 AN: 33478

South Asian (SAS) AF: 0.00 AC: 0 AN: 75530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35688

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4702

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1067664

Other (OTH) AF: 0.00 AC: 0 AN: 56400

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152038 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74252

African (AFR) AF: 0.0000241 AC: 1 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10600

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.25	N
LIST_S2	Uncertain	0.86	D
M_CAP	Pathogenic	0.96	D
MetaRNN	Benign	0.24	T
MetaSVM	Uncertain	-0.11	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.3
PrimateAI	Pathogenic	0.90	D
PROVEAN	Benign	-0.67	N
REVEL	Benign	0.20
Sift	Benign	0.48	T
Sift4G	Benign	0.57	T
Polyphen		0.032	B
Vest4		0.16
MutPred		0.32		Gain of catalytic residue at A91 (P = 0.001)
MVP		0.85
MPC		0.87
ClinPred		0.17	T
GERP RS		2.2
PromoterAI		-0.014	Neutral
Varity_R		0.044
gMVP		0.24
Mutation Taster		=84/16	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: rs1187256678; hg19: chr12-54332962;