Variant 12-54000713-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_006897.3(HOXC9):c.525C>T(p.Ala175=) 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.950

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:

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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/exons	MANE	UniProt
HOXC9	NM_006897.3 linkuse as main transcript	c.525C>T	p.Ala175=	synonymous_variant	1/2	ENST00000303450.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXC9	ENST00000303450.5 linkuse as main transcript	c.525C>T	p.Ala175=	synonymous_variant	1/2	1	NM_006897.3	P1

Frequencies

GnomAD3 genomes

AF:

0.554

AC:

84258

AN:

152032

Hom.:

23672

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.592

AC:

104243

AN:

176062

Hom.:

30576

AF XY:

0.592

AC XY:

58560

AN XY:

98918

show subpopulations

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 SAS exome

AF:

0.590

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.:

AF XY:

0.588

AC XY:

405059

AN XY:

689244

show subpopulations

Gnomad4 AFR exome

AF:

0.486

Gnomad4 AMR exome

AF:

0.530

Gnomad4 ASJ exome

AF:

0.567

Gnomad4 EAS exome

AF:

0.728

Gnomad4 SAS exome

AF:

0.577

Gnomad4 FIN exome

AF:

0.542

Gnomad4 NFE exome

AF:

0.591

Gnomad4 OTH exome

AF:

0.593

GnomAD4 genome

AF:

0.554

AC:

84278

AN:

152148

Hom.:

23675

Cov.:

AF XY:

0.552

AC XY:

41074

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.490

Gnomad4 AMR

AF:

0.546

Gnomad4 ASJ

AF:

0.558

Gnomad4 EAS

AF:

0.763

Gnomad4 SAS

AF:

0.566

Gnomad4 FIN

AF:

0.531

Gnomad4 NFE

AF:

0.581

Gnomad4 OTH

AF:

0.578

Alfa

AF:

0.568

Hom.:

38944

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

DANN

Benign

0.96

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