chr12-54000713-C-T

Variant names:

• chr12-54000713-C-T
• rs2241820
• NM_006897.3:c.525C>T

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_006897.3(HOXC9):​c.525C>T​(p.Ala175Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 1,544,930 control chromosomes in the GnomAD database, including 265,748 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 0.55 (23675 hom., cov: 33)
  • Exomes 𝑓: 0.59 (242073 hom.)
• Consequence: HOXC9 NM_006897.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.950
• Publications: 24 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=-0.41).
• BP7: Synonymous conserved (PhyloP=0.95 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXC9	NM_006897.3	c.525C>T	p.Ala175Ala	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.525C>T	p.Ala175Ala	synonymous_variant	Exon 1 of 2	1	NM_006897.3	ENSP00000302836.4
ENSG00000273049	ENST00000513209.1	c.166+14703C>T		intron_variant	Intron 1 of 1	3		ENSP00000476742.1

Frequencies

GnomAD3 genomes AF: 0.554 AC: 84258 AN: 152032 Hom.: 23672 Cov.: 33

Gnomad AFR AF: 0.490

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.763

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.585

GnomAD2 exomes AF: 0.592 AC: 104243 AN: 176062 AF XY: 0.592

Gnomad AFR exome AF: 0.524

Gnomad AMR exome AF: 0.535

Gnomad ASJ exome AF: 0.578

Gnomad EAS exome AF: 0.781

Gnomad FIN exome AF: 0.546

Gnomad NFE exome AF: 0.598

Gnomad OTH exome AF: 0.590

GnomAD4 exome AF: 0.588 AC: 819390 AN: 1392782 Hom.: 242073 Cov.: 49 AF XY: 0.588 AC XY: 405059 AN XY: 689244

African (AFR) AF: 0.486 AC: 13909 AN: 28628

American (AMR) AF: 0.530 AC: 17461 AN: 32928

Ashkenazi Jewish (ASJ) AF: 0.567 AC: 13289 AN: 23418

East Asian (EAS) AF: 0.728 AC: 26299 AN: 36114

South Asian (SAS) AF: 0.577 AC: 45188 AN: 78362

European-Finnish (FIN) AF: 0.542 AC: 25840 AN: 47646

Middle Eastern (MID) AF: 0.623 AC: 2537 AN: 4072

European-Non Finnish (NFE) AF: 0.591 AC: 640906 AN: 1084362

Other (OTH) AF: 0.593 AC: 33961 AN: 57252

GnomAD4 genome AF: 0.554 AC: 84278 AN: 152148 Hom.: 23675 Cov.: 33 AF XY: 0.552 AC XY: 41074 AN XY: 74362

African (AFR) AF: 0.490 AC: 20327 AN: 41518

American (AMR) AF: 0.546 AC: 8349 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1937 AN: 3472

East Asian (EAS) AF: 0.763 AC: 3929 AN: 5150

South Asian (SAS) AF: 0.566 AC: 2732 AN: 4826

European-Finnish (FIN) AF: 0.531 AC: 5625 AN: 10584

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.581 AC: 39474 AN: 67976

Other (OTH) AF: 0.578 AC: 1223 AN: 2116

Alfa AF: 0.569 Hom.: 93080

Bravo AF: 0.554

Asia WGS AF: 0.594 AC: 2067 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
CADD	Benign	15
DANN	Benign	0.96
PhyloP100		0.95
Mutation Taster		=100/0	polymorphism (auto)

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: rs2241820; hg19: chr12-54394497; COSMIC: COSV57716566; COSMIC: COSV57716566;