12-54006444-C-A

Position:

• chr12-54006444-C-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000509328.1(HOXC6):​c.-73+11428C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 152,284 control chromosomes in the GnomAD database, including 1,452 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1452 hom., cov: 33)
• Consequence: HOXC6 ENST00000509328.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.25

Genes affected

HOXC6 (HGNC:5128): (homeobox C6) This gene belongs to the homeobox family, members of which 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, HOXC6, is one of several HOXC genes located in a cluster on chromosome 12. Three genes, HOXC5, HOXC4 and HOXC6, share a 5' non-coding exon. Transcripts may include the shared exon spliced to the gene-specific exons, or they may include only the gene-specific exons. Alternatively spliced transcript variants encoding different isoforms have been identified for HOXC6. Transcript variant two includes the shared exon, and transcript variant one includes only gene-specific exons. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXC6	ENST00000504315.1	c.-193+15630C>A		intron_variant		3		ENSP00000424124
HOXC6	ENST00000509328.1	c.-73+11428C>A		intron_variant		3		ENSP00000423898

Frequencies

GnomAD3 genomes AF: 0.127 AC: 19366 AN: 152166 Hom.: 1457 Cov.: 33

Gnomad AFR AF: 0.0553

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.147

Gnomad EAS AF: 0.223

Gnomad SAS AF: 0.228

Gnomad FIN AF: 0.0796

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.154

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.127 AC: 19350 AN: 152284 Hom.: 1452 Cov.: 33 AF XY: 0.125 AC XY: 9287 AN XY: 74470

Gnomad4 AFR AF: 0.0553

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.147

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.228

Gnomad4 FIN AF: 0.0796

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.151

Alfa AF: 0.152 Hom.: 1189

Bravo AF: 0.126

Asia WGS AF: 0.214 AC: 746 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	19
DANN	Benign	0.91

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

LitVar

Other links and lift over

dbSNP: rs12822416; hg19: chr12-54400228;