12-53939019-G-T

Variant names:

• chr12-53939019-G-T
• rs771034781
• NM_017410.3:c.113G>T

Variant summary

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

The NM_017410.3(HOXC13):​c.113G>T​(p.Gly38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000075 in 1,333,288 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. G38D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: HOXC13 NM_017410.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.911
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.113G>T	p.Gly38Val	missense	Exon 1 of 2	NP_059106.2
	HOXC13-AS	NR_047507.1		n.173+452C>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.113G>T	p.Gly38Val	missense	Exon 1 of 2	ENSP00000243056.3	P31276
	HOXC13-AS	ENST00000512916.3	TSL:3	n.222+452C>A		intron	N/A
	HOXC13-AS	ENST00000810609.1		n.181+452C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.50e-7 AC: 1 AN: 1333288 Hom.: 0 Cov.: 33 AF XY: 0.00000152 AC XY: 1 AN XY: 656426

African (AFR) AF: 0.00 AC: 0 AN: 27106

American (AMR) AF: 0.00 AC: 0 AN: 29422

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22802

East Asian (EAS) AF: 0.00 AC: 0 AN: 30606

South Asian (SAS) AF: 0.0000136 AC: 1 AN: 73490

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33330

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4606

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1056472

Other (OTH) AF: 0.00 AC: 0 AN: 55454

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Uncertain	0.071	D
BayesDel_noAF	Benign	-0.14
CADD	Benign	19
DANN	Benign	0.91
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.71	D
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Uncertain	0.55	D
MetaSVM	Uncertain	-0.13	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.91
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	0.0	N
REVEL	Uncertain	0.34
Sift	Benign	0.15	T
Sift4G	Uncertain	0.012	D
Polyphen		0.50	P
Vest4		0.45
MutPred		0.31		Gain of catalytic residue at A42 (P = 0)
MVP		0.91
MPC		2.0
ClinPred		0.26	T
GERP RS		2.9
PromoterAI		0.11	Neutral
Varity_R		0.15
gMVP		0.40
Mutation Taster		=91/9	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: rs771034781; hg19: chr12-54332803;