chr12-54000553-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006897.3(HOXC9):c.365C>T(p.Ala122Val) variant causes a missense change. The variant allele was found at a frequency of 0.00319 in 1,545,436 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 52 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 57 hom. )

Consequence

HOXC9
NM_006897.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.51

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0031582415).

BP6

Variant 12-54000553-C-T is Benign according to our data. Variant chr12-54000553-C-T is described in ClinVar as [Benign]. Clinvar id is 776712.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXC9	NM_006897.3 link	c.365C>T	p.Ala122Val	missense_variant	Exon 1 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.365C>T	p.Ala122Val	missense_variant	Exon 1 of 2	1	NM_006897.3	ENSP00000302836.4		P31274
ENSG00000273049	ENST00000513209.1 link	c.166+14543C>T		intron_variant	Intron 1 of 1	3		ENSP00000476742.1		V9GYH0

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2296

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0508

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00772

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0255

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.0124

GnomAD2 exomes

AF:

0.00455

AC:

651

AN:

143122

AF XY:

0.00353

show subpopulations

Gnomad AFR exome

AF:

0.0664

Gnomad AMR exome

AF:

0.00471

Gnomad ASJ exome

AF:

0.00175

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000462

Gnomad OTH exome

AF:

0.00382

GnomAD4 exome

AF:

0.00189

AC:

2628

AN:

1393090

Hom.:

Cov.:

AF XY:

0.00175

AC XY:

1206

AN XY:

689504

show subpopulations

Gnomad4 AFR exome

AF:

0.0565

AC:

1779

AN:

31470

Gnomad4 AMR exome

AF:

0.00508

AC:

177

AN:

34816

Gnomad4 ASJ exome

AF:

0.00176

AC:

AN:

24992

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

36268

Gnomad4 SAS exome

AF:

0.000248

AC:

AN:

80794

Gnomad4 FIN exome

AF:

0.0000275

AC:

AN:

36398

Gnomad4 NFE exome

AF:

0.000291

AC:

316

AN:

1084974

Gnomad4 Remaining exome

AF:

0.00427

AC:

248

AN:

58032

Heterozygous variant carriers

153

306

458

611

764

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

140

210

280

350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0151

AC:

2301

AN:

152346

Hom.:

Cov.:

AF XY:

0.0144

AC XY:

1071

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.0507

AC:

0.050748

AN:

0.050748

Gnomad4 AMR

AF:

0.00771

AC:

0.00770738

AN:

0.00770738

Gnomad4 ASJ

AF:

0.00144

AC:

0.00144092

AN:

0.00144092

Gnomad4 EAS

AF:

0.00

AC:

AN:

Gnomad4 SAS

AF:

0.00

AC:

AN:

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000500

AC:

0.00049975

AN:

0.00049975

Gnomad4 OTH

AF:

0.0123

AC:

0.0122873

AN:

0.0122873

Heterozygous variant carriers

129

258

387

516

645

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00668

Hom.:

Bravo

AF:

0.0175

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.0381

AC:

117

ESP6500EA

AF:

0.000913

AC:

ExAC

AF:

0.00389

AC:

414

Asia WGS

AF:

0.00549

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 14, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.17

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.077

T;T

Eigen

Benign

-0.040

Eigen_PC

Benign

0.11

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.81

.;T

MetaRNN

Benign

0.0032

T;T

MetaSVM

Benign

-0.36

MutationAssessor

Benign

1.0

L;L

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.0

N;N

REVEL

Uncertain

0.30

Sift

Benign

0.33

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.034

B;B

Vest4

0.56

MVP

0.92

MPC

0.89

ClinPred

0.011

GERP RS

4.0

Varity_R

0.20

Mutation Taster

=97/3

polymorphism

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over