11-99819690-A-T

Variant names:

• chr11-99819690-A-T
• rs753357501
• NM_014361.4:c.202A>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.202A>T​(p.Ser68Cys) 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. 17/22 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. S68G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 54)
• Consequence: CNTN5 NM_014361.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81
• 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=0.14102307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CNTN5	NM_014361.4	c.202A>T	p.Ser68Cys	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.202A>T	p.Ser68Cys	missense_variant	Exon 4 of 25	1	NM_014361.4	ENSP00000435637.1

Frequencies

GnomAD3 genomes Cov.: 54

GnomAD4 exome Cov.: 65

GnomAD4 genome Cov.: 54

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.91
DEOGEN2	Benign	0.36	.;T;T;T
Eigen	Benign	-0.59
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.65	T;.;T;T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;L;.
PhyloP100		1.8
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.28	N;N;N;.
REVEL	Benign	0.15
Sift	Uncertain	0.019	D;D;D;.
Sift4G	Benign	0.075	T;T;T;T
Polyphen		0.21	.;B;B;.
Vest4		0.47
MutPred		0.48		Loss of disorder (P = 0.0132);Loss of disorder (P = 0.0132);Loss of disorder (P = 0.0132);.;
MVP		0.55
MPC		0.13
ClinPred		0.37	T
GERP RS		1.6
PromoterAI		0.0025	Neutral
Varity_R		0.085
gMVP		0.26
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: rs753357501; hg19: chr11-99690421;