Variant chr12-53975224-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014212.4(HOXC11):c.726C>G(p.Phe242Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000175 in 1,611,760 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

HOXC11
NM_014212.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39

Variant links:

Genes affected

HOXC11 (HGNC:5123): (homeobox C11) 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. The product of this gene binds to a promoter element of the lactase-phlorizin hydrolase. It also may play a role in early intestinal development. An alternatively spliced variant encoding a shorter isoform has been described but its full-length nature has not been determined. [provided by RefSeq, Jul 2008]

HOXC11 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08669093).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXC11	NM_014212.4 linkuse as main transcript	c.726C>G	p.Phe242Leu	missense_variant	2/2	ENST00000546378.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXC11	ENST00000546378.1 linkuse as main transcript	c.726C>G	p.Phe242Leu	missense_variant	2/2	1	NM_014212.4	P1
HOXC11	ENST00000243082.4 linkuse as main transcript	c.730C>G	p.Pro244Ala	missense_variant	2/2	3

Frequencies

GnomAD3 genomes

AF:

0.000184

AC:

AN:

151886

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000484

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000212

AC:

AN:

250048

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

135550

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00200

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000274

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000174

AC:

254

AN:

1459756

Hom.:

Cov.:

AF XY:

0.000198

AC XY:

144

AN XY:

726150

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00184

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000171

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000184

AC:

AN:

152004

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000447

Hom.:

Bravo

AF:

0.000200

ExAC

AF:

0.000198

AC:

EpiCase

AF:

0.000273

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2021

The c.726C>G (p.F242L) alteration is located in exon 2 (coding exon 2) of the HOXC11 gene. This alteration results from a C to G substitution at nucleotide position 726, causing the phenylalanine (F) at amino acid position 242 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.99

BayesDel_addAF

Benign

-0.038

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.61

Eigen

Benign

-0.12

Eigen_PC

Benign

-0.022

FATHMM_MKL

Uncertain

0.80

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.023

MetaRNN

Benign

0.087

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.015

MutationTaster

Benign

1.0

D;N

PrimateAI

Pathogenic

0.92

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.48

Sift

Uncertain

0.0020

Sift4G

Benign

0.12

Polyphen

0.0010

Vest4

0.41

MutPred

0.30

Loss of methylation at K241 (P = 0.0297);

MVP

0.94

ClinPred

0.15

GERP RS

2.5

Varity_R

0.82

gMVP

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.15

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