Genetic Variant NM_014212.4:c.569C>G (chr12-53973810-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_014212.4(HOXC11):c.569C>G(p.Ala190Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

HOXC11
NM_014212.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.816

Publications

0 publications found

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:

HOTAIR (HGNC:33510): (HOX transcript antisense RNA) This gene is located within the Homeobox C (HOXC) gene cluster on chromosome 12 and is co-expressed with the HOXC genes. It functions through an RNA product, which binds lysine specific demethylase 1 (LSD1) and Polycomb repressive complex 2 (PRC2), and serves as a scaffold to assemble these regulators at the HOXD gene cluster, thereby promoting epigenetic repression of HOXD. This gene is highly expressed in multiple tumors. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Feb 2019]

HOTAIR links:

ENSG00000293681 (HGNC:):

ENSG00000293681 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08428672).

BP6

Variant 12-53973810-C-G is Benign according to our data. Variant chr12-53973810-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2374769.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014212.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXC11	NM_014212.4	MANE Select	c.569C>G	p.Ala190Gly	missense	Exon 1 of 2	NP_055027.1	O43248
HOTAIR	NR_186241.1	MANE Select	n.57+1088G>C		intron	N/A
HOTAIR	NR_047517.2		n.57+1088G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
HOXC11	ENST00000546378.1	TSL:1 MANE Select	c.569C>G	p.Ala190Gly	missense	Exon 1 of 2	ENSP00000446680.1	O43248
HOTAIR	ENST00000424518.6	TSL:5 MANE Select	n.57+1088G>C		intron	N/A
HOXC11	ENST00000243082.4	TSL:3	c.569C>G	p.Ala190Gly	missense	Exon 1 of 2	ENSP00000243082.4	J3KMZ0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1375606

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

682496

African (AFR)

AF:

0.00

AC:

AN:

30412

American (AMR)

AF:

0.00

AC:

AN:

32682

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22932

East Asian (EAS)

AF:

0.00

AC:

AN:

36870

South Asian (SAS)

AF:

0.00

AC:

AN:

79928

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5382

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1065360

Other (OTH)

AF:

0.00

AC:

AN:

56090

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.024

Eigen

Benign

-0.98

Eigen_PC

Benign

-0.84

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.17

M_CAP

Uncertain

0.22

MetaRNN

Benign

0.084

MetaSVM

Benign

-0.51

MutationAssessor

Benign

0.0

PhyloP100

0.82

PrimateAI

Uncertain

0.68

PROVEAN

Benign

-1.1

REVEL

Benign

0.14

Sift

Benign

0.25

Sift4G

Benign

0.39

Polyphen

0.0040

Vest4

0.036

MutPred

0.29

Gain of catalytic residue at G188 (P = 0.0032)

MVP

0.79

ClinPred

0.082

GERP RS

2.4

Varity_R

0.086

gMVP

0.41

Mutation Taster

=85/15

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over