chr12-54000500-C-T

Variant names:

• chr12-54000500-C-T
• rs34079606
• NM_006897.3:c.312C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BS1 BS2

The NM_006897.3(HOXC9):​c.312C>T​(p.Val104Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0231 in 1,598,652 control chromosomes in the GnomAD database, including 473 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 0.018 (39 hom., cov: 33)
  • Exomes 𝑓: 0.024 (434 hom.)
• Consequence: HOXC9 NM_006897.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.495
• Publications: 2 publications found

Genes affected

HOXC9 (HGNC:5130): (homeobox C9) 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. [provided by RefSeq, Jul 2008]

ENSG00000273049 (HGNC:):

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

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP7: Synonymous conserved (PhyloP=0.495 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0179 (2723/152360) while in subpopulation NFE AF = 0.0262 (1781/68020). AF 95% confidence interval is 0.0252. There are 39 homozygotes in GnomAd4. There are 1333 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2723 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXC9	NM_006897.3	c.312C>T	p.Val104Val	synonymous_variant	Exon 1 of 2	ENST00000303450.5	NP_008828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXC9	ENST00000303450.5	c.312C>T	p.Val104Val	synonymous_variant	Exon 1 of 2	1	NM_006897.3	ENSP00000302836.4
ENSG00000273049	ENST00000513209.1	c.166+14490C>T		intron_variant	Intron 1 of 1	3		ENSP00000476742.1

Frequencies

GnomAD3 genomes AF: 0.0179 AC: 2727 AN: 152244 Hom.: 39 Cov.: 33

Gnomad AFR AF: 0.00417

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.00739

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.0170

Gnomad SAS AF: 0.0221

Gnomad FIN AF: 0.0325

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0262

Gnomad OTH AF: 0.0110

GnomAD2 exomes AF: 0.0196 AC: 4405 AN: 224980 AF XY: 0.0206

Gnomad AFR exome AF: 0.00426

Gnomad AMR exome AF: 0.00461

Gnomad ASJ exome AF: 0.0157

Gnomad EAS exome AF: 0.0187

Gnomad FIN exome AF: 0.0306

Gnomad NFE exome AF: 0.0255

Gnomad OTH exome AF: 0.0152

GnomAD4 exome AF: 0.0236 AC: 34157 AN: 1446292 Hom.: 434 Cov.: 31 AF XY: 0.0236 AC XY: 16962 AN XY: 719920

African (AFR) AF: 0.00302 AC: 101 AN: 33404

American (AMR) AF: 0.00472 AC: 210 AN: 44452

Ashkenazi Jewish (ASJ) AF: 0.0171 AC: 444 AN: 26040

East Asian (EAS) AF: 0.0137 AC: 540 AN: 39560

South Asian (SAS) AF: 0.0212 AC: 1820 AN: 85968

European-Finnish (FIN) AF: 0.0294 AC: 1183 AN: 40216

Middle Eastern (MID) AF: 0.00868 AC: 50 AN: 5760

European-Non Finnish (NFE) AF: 0.0257 AC: 28544 AN: 1110844

Other (OTH) AF: 0.0211 AC: 1265 AN: 60048

GnomAD4 genome AF: 0.0179 AC: 2723 AN: 152360 Hom.: 39 Cov.: 33 AF XY: 0.0179 AC XY: 1333 AN XY: 74508

African (AFR) AF: 0.00416 AC: 173 AN: 41602

American (AMR) AF: 0.00738 AC: 113 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.0187 AC: 65 AN: 3470

East Asian (EAS) AF: 0.0170 AC: 88 AN: 5172

South Asian (SAS) AF: 0.0219 AC: 106 AN: 4834

European-Finnish (FIN) AF: 0.0325 AC: 345 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0262 AC: 1781 AN: 68020

Other (OTH) AF: 0.0104 AC: 22 AN: 2116

Alfa AF: 0.0215 Hom.: 8

Bravo AF: 0.0152

Asia WGS AF: 0.0140 AC: 50 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.96
PhyloP100		0.49
PromoterAI		0.092	Neutral
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs34079606; hg19: chr12-54394284; COSMIC: COSV57716951; COSMIC: COSV57716951;