11-99844884-G-A

Position:

• chr11-99844884-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014361.4(CNTN5):​c.310G>A​(p.Glu104Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTN5 NM_014361.4 missense
• Clinical Significance: Uncertain significance no assertion criteria provided U:1
• Conservation: PhyloP100: 9.07

Genes affected

CNTN5 (HGNC:2175): (contactin 5) The protein encoded by this gene is a member of the immunoglobulin superfamily, and contactin family, which mediate cell surface interactions during nervous system development. This protein 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. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN5	NM_014361.4	c.310G>A	p.Glu104Lys	missense_variant	5/25	ENST00000524871.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN5	ENST00000524871.6	c.310G>A	p.Glu104Lys	missense_variant	5/25	1	NM_014361.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

Submissions by phenotype

CNTN5-related disorder Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 15, 2024

The CNTN5 c.310G>A variant is predicted to result in the amino acid substitution p.Glu104Lys. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.51
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	31
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.29	.;T;T;.;T;.
Eigen	Pathogenic	0.76
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;.;D;D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.66	D;D;D;D;D;D
MetaSVM	Benign	-0.35	T
MutationAssessor	Benign	0.91	L;L;L;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-2.1	N;N;N;N;.;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.0020	D;D;D;D;.;.
Sift4G	Uncertain	0.0040	D;D;D;D;D;D
Polyphen		1.0	.;D;D;D;.;.
Vest4		0.87
MutPred		0.46		Gain of methylation at E104 (P = 0.0062);Gain of methylation at E104 (P = 0.0062);Gain of methylation at E104 (P = 0.0062);.;.;.;
MVP		0.83
MPC		0.28
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.49
gMVP		0.75

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: chr11-99715616;