rs768030519

Variant names:

• chr11-99819723-C-A
• rs768030519
• NM_014361.4:c.235C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-99819723-C-A
• chr11-99819723-C-G
• chr11-99819723-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014361.4(CNTN5):​c.235C>A​(p.Pro79Thr) 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. 13/22 in silico tools predict a benign outcome for this variant. 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. P79S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 55)
• Consequence: CNTN5 NM_014361.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21594283).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN5	NM_014361.4	c.235C>A	p.Pro79Thr	missense_variant	Exon 4 of 25	ENST00000524871.6	NP_055176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CNTN5	ENST00000524871.6	c.235C>A	p.Pro79Thr	missense_variant	Exon 4 of 25	1	NM_014361.4	ENSP00000435637.1

Frequencies

GnomAD3 genomes Cov.: 55

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 55

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.14	.;T;T;T
Eigen	Benign	0.036
Eigen_PC	Benign	0.048
FATHMM_MKL	Benign	0.76	D
LIST_S2	Benign	0.75	T;.;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	2.0	M;M;M;.
PhyloP100		2.2
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	0.37	N;N;N;.
REVEL	Benign	0.20
Sift	Uncertain	0.019	D;D;D;.
Sift4G	Uncertain	0.055	T;T;T;T
Polyphen		0.86	.;P;P;.
Vest4		0.71
MutPred		0.37		Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);Loss of sheet (P = 0.1158);.;
MVP		0.79
MPC		0.082
ClinPred		0.57	D
GERP RS		4.1
PromoterAI		0.014	Neutral
Varity_R		0.096
gMVP		0.44
Mutation Taster		=94/6	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: rs768030519; hg19: chr11-99690454; COSMIC: COSV54364592;