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GeneBe

3-1227930-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001289080.2(CNTN6):c.295C>A(p.Gln99Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CNTN6
NM_001289080.2 missense

Scores

2
9
7

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.33
Variant links:
Genes affected
CNTN6 (HGNC:2176): (contactin 6) The protein encoded by this gene is a member of the immunoglobulin superfamily. It is a glycosylphosphatidylinositol (GPI)-anchored neuronal membrane protein that functions as a cell adhesion molecule. It may play a role in the formation of axon connections in the developing nervous system. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.826

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CNTN6NM_001289080.2 linkuse as main transcriptc.295C>A p.Gln99Lys missense_variant 4/23 ENST00000446702.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CNTN6ENST00000446702.7 linkuse as main transcriptc.295C>A p.Gln99Lys missense_variant 4/231 NM_001289080.2 P1
CNTN6ENST00000350110.2 linkuse as main transcriptc.295C>A p.Gln99Lys missense_variant 4/231 P1
CNTN6ENST00000394261.2 linkuse as main transcriptc.*273C>A 3_prime_UTR_variant, NMD_transcript_variant 5/81
CNTN6ENST00000397479.6 linkuse as main transcriptc.*433C>A 3_prime_UTR_variant, NMD_transcript_variant 3/222

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsMar 01, 2024The c.295C>A (p.Q99K) alteration is located in exon 4 (coding exon 3) of the CNTN6 gene. This alteration results from a C to A substitution at nucleotide position 295, causing the glutamine (Q) at amino acid position 99 to be replaced by a lysine (K). 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
Uncertain
0.52
BayesDel_addAF
Uncertain
0.085
D
BayesDel_noAF
Benign
-0.12
Cadd
Uncertain
25
Dann
Uncertain
1.0
DEOGEN2
Benign
0.33
T;T
Eigen
Uncertain
0.65
Eigen_PC
Uncertain
0.62
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.040
D
MetaRNN
Pathogenic
0.83
D;D
MetaSVM
Benign
-0.46
T
MutationAssessor
Benign
1.7
L;L
MutationTaster
Benign
1.0
D;D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Uncertain
-2.7
D;D
REVEL
Benign
0.27
Sift
Uncertain
0.011
D;D
Sift4G
Uncertain
0.025
D;D
Polyphen
0.98
D;D
Vest4
0.85
MutPred
0.60
Gain of methylation at Q99 (P = 0.0025);Gain of methylation at Q99 (P = 0.0025);
MVP
0.76
MPC
0.019
ClinPred
0.98
D
GERP RS
5.5
Varity_R
0.44
gMVP
0.72

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-1269614; API