chr11-99844951-G-T

Variant names:

• chr11-99844951-G-T
• rs200429080
• NM_014361.4:c.377G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_014361.4(CNTN5):​c.377G>T​(p.Arg126Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R126H) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTN5 NM_014361.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.09
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN5	NM_014361.4	c.377G>T	p.Arg126Leu	missense_variant	Exon 5 of 25	ENST00000524871.6	NP_055176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN5	ENST00000524871.6	c.377G>T	p.Arg126Leu	missense_variant	Exon 5 of 25	1	NM_014361.4	ENSP00000435637.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.35	.;T;T;.;T;.
Eigen	Benign	0.043
Eigen_PC	Benign	-0.037
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.73	T;.;T;T;T;T
M_CAP	Benign	0.053	D
MetaRNN	Uncertain	0.58	D;D;D;D;D;D
MetaSVM	Benign	-0.57	T
MutationAssessor	Benign	0.99	L;L;L;.;.;.
PhyloP100		3.1
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-4.4	D;D;D;D;.;.
REVEL	Uncertain	0.42
Sift	Uncertain	0.0020	D;D;D;D;.;.
Sift4G	Uncertain	0.013	D;D;D;D;D;D
Polyphen		0.99, 0.84	.;D;D;P;.;.
Vest4		0.55
MutPred		0.42		Loss of solvent accessibility (P = 0.1144);Loss of solvent accessibility (P = 0.1144);Loss of solvent accessibility (P = 0.1144);.;.;.;
MVP		0.80
MPC		0.24
ClinPred		0.99	D
GERP RS		2.5
Varity_R		0.47
gMVP		0.70
Mutation Taster		=85/15	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

Other links and lift over

dbSNP: rs200429080; hg19: chr11-99715683;