Variant rs753499438 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006897.3(HOXC9):c.555C>A(p.Asn185Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Consequence

HOXC9
NM_006897.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.956

Variant links:

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]

HOXC9 links:

ENSG00000273049 (HGNC:):

ENSG00000273049 links:

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]

HOXC6 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.774

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXC9	NM_006897.3 link	c.555C>A	p.Asn185Lys	missense_variant	Exon 2 of 2	ENST00000303450.5	NP_008828.1	P31274A0A024RAZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXC9	ENST00000303450.5 link	c.555C>A	p.Asn185Lys	missense_variant	Exon 2 of 2	1	NM_006897.3	ENSP00000302836.4		P31274
ENSG00000273049	ENST00000513209.1 link	c.166+16436C>A		intron_variant	Intron 1 of 1	3		ENSP00000476742.1		V9GYH0

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000162

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.46

T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.82

LIST_S2

Pathogenic

0.98

.;D

M_CAP

Pathogenic

0.38

MetaRNN

Pathogenic

0.77

D;D

MetaSVM

Pathogenic

0.83

MutationAssessor

Benign

1.8

L;L

PrimateAI

Pathogenic

0.84

PROVEAN

Pathogenic

-4.6

D;D

REVEL

Uncertain

0.64

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.012

D;D

Polyphen

1.0

D;D

Vest4

0.78

MutPred

0.46

Gain of methylation at N185 (P = 0.001);Gain of methylation at N185 (P = 0.001);

MVP

0.99

MPC

2.0

ClinPred

0.99

GERP RS

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Varity_R

0.74

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over