rs771034781

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr12-53939019-G-A
• chr12-53939019-G-T

Variant summary

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

The NM_017410.3(HOXC13):​c.113G>A​(p.Gly38Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000101 in 1,485,308 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G38S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: HOXC13 NM_017410.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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 0 ACMG points.

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>A	p.Gly38Asp	missense	Exon 1 of 2	NP_059106.2
	HOXC13-AS	NR_047507.1		n.173+452C>T		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>A	p.Gly38Asp	missense	Exon 1 of 2	ENSP00000243056.3	P31276
	HOXC13-AS	ENST00000512916.3	TSL:3	n.222+452C>T		intron	N/A
	HOXC13-AS	ENST00000810609.1		n.181+452C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000395 AC: 6 AN: 152020 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

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: 0.0000883

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000703 AC: 6 AN: 85306 AF XY: 0.000104

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000230

Gnomad NFE exome AF: 0.000155

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000108 AC: 144 AN: 1333288 Hom.: 0 Cov.: 33 AF XY: 0.0000945 AC XY: 62 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: 0.00 AC: 0 AN: 73490

European-Finnish (FIN) AF: 0.0000600 AC: 2 AN: 33330

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

European-Non Finnish (NFE) AF: 0.000128 AC: 135 AN: 1056472

Other (OTH) AF: 0.000126 AC: 7 AN: 55454

GnomAD4 genome AF: 0.0000395 AC: 6 AN: 152020 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74264

African (AFR) AF: 0.00 AC: 0 AN: 41394

American (AMR) AF: 0.00 AC: 0 AN: 15270

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000883 AC: 6 AN: 67950

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000872 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000451 AC: 4

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	0.21
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.47	T
M_CAP	Pathogenic	0.97	D
MetaRNN	Uncertain	0.52	D
MetaSVM	Benign	-0.28	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.91
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	-0.28	N
REVEL	Uncertain	0.36
Sift	Benign	0.42	T
Sift4G	Uncertain	0.020	D
Polyphen		0.22	B
Vest4		0.46
MVP		0.89
MPC		2.0
ClinPred		0.088	T
GERP RS		2.9
PromoterAI		0.029	Neutral
Varity_R		0.11
gMVP		0.48
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;