Variant rs34079606 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.495

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 Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2723 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXC9	NM_006897.3 linkuse as main transcript	c.312C>T	p.Val104Val	synonymous_variant	1/2	ENST00000303450.5	NP_008828.1	P31274A0A024RAZ6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
HOXC9	ENST00000303450.5 linkuse as main transcript	c.312C>T	p.Val104Val	synonymous_variant	1/2	1	NM_006897.3	ENSP00000302836.4		P31274
ENSG00000273049	ENST00000513209.1 linkuse as main transcript	c.166+14490C>T		intron_variant		3		ENSP00000476742.1		V9GYH0

Frequencies

GnomAD3 genomes

AF:

0.0179

AC:

2727

AN:

152244

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0196

AC:

4405

AN:

224980

Hom.:

AF XY:

0.0206

AC XY:

2582

AN XY:

125072

show subpopulations

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 SAS exome

AF:

0.0211

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.:

AF XY:

0.0236

AC XY:

16962

AN XY:

719920

show subpopulations

Gnomad4 AFR exome

AF:

0.00302

Gnomad4 AMR exome

AF:

0.00472

Gnomad4 ASJ exome

AF:

0.0171

Gnomad4 EAS exome

AF:

0.0137

Gnomad4 SAS exome

AF:

0.0212

Gnomad4 FIN exome

AF:

0.0294

Gnomad4 NFE exome

AF:

0.0257

Gnomad4 OTH exome

AF:

0.0211

GnomAD4 genome

AF:

0.0179

AC:

2723

AN:

152360

Hom.:

Cov.:

AF XY:

0.0179

AC XY:

1333

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.00416

Gnomad4 AMR

AF:

0.00738

Gnomad4 ASJ

AF:

0.0187

Gnomad4 EAS

AF:

0.0170

Gnomad4 SAS

AF:

0.0219

Gnomad4 FIN

AF:

0.0325

Gnomad4 NFE

AF:

0.0262

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0215

Hom.:

Bravo

AF:

0.0152

Asia WGS

AF:

0.0140

AC:

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

DANN

Benign

0.96

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

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