rs780011888

Variant names:

• chr12-54002570-C-G
• rs780011888
• NM_006897.3:c.679C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-54002570-C-G
• chr12-54002570-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006897.3(HOXC9):​c.679C>G​(p.Arg227Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. R227W) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: HOXC9 NM_006897.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 0 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: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.903

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXC9	NM_006897.3	c.679C>G	p.Arg227Gly	missense_variant	Exon 2 of 2	ENST00000303450.5	NP_008828.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXC9	ENST00000303450.5	c.679C>G	p.Arg227Gly	missense_variant	Exon 2 of 2	1	NM_006897.3	ENSP00000302836.4
ENSG00000273049	ENST00000513209.1	c.166+16560C>G		intron_variant	Intron 1 of 1	3		ENSP00000476742.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.90
BayesDel_addAF	Pathogenic	0.46	D
BayesDel_noAF	Pathogenic	0.42
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Pathogenic	0.82	D;D
Eigen	Uncertain	0.36
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.65	D
LIST_S2	Uncertain	0.91	.;D
M_CAP	Pathogenic	0.49	D
MetaRNN	Pathogenic	0.90	D;D
MetaSVM	Pathogenic	0.85	D
MutationAssessor	Benign	1.8	L;L
PhyloP100		1.3
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-5.4	D;D
REVEL	Pathogenic	0.75
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.99	D;D
Vest4		0.90
MutPred		0.60		Gain of catalytic residue at V228 (P = 9e-04);Gain of catalytic residue at V228 (P = 9e-04);
MVP		0.99
MPC		2.1
ClinPred		0.98	D
GERP RS		4.1
Varity_R		0.82
Mutation Taster		=48/52	disease causing

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: rs780011888; hg19: chr12-54396354;