11-99956961-A-G

Position:

• chr11-99956961-A-G

Variant summary

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

The NM_014361.4(CNTN5):​c.829A>G​(p.Asn277Asp) 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 (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CNTN5 NM_014361.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.94

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	Protein	UniProt
CNTN5	NM_014361.4	c.829A>G	p.Asn277Asp	missense_variant	8/25	ENST00000524871.6	NP_055176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CNTN5	ENST00000524871.6	c.829A>G	p.Asn277Asp	missense_variant	8/25	1	NM_014361.4	ENSP00000435637.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 26, 2023

The c.829A>G (p.N277D) alteration is located in exon 1 (coding exon 1) of the CNTN5 gene. This alteration results from a A to G substitution at nucleotide position 829, causing the asparagine (N) at amino acid position 277 to be replaced by an aspartic acid (D). 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	Benign	0.19
BayesDel_addAF	Uncertain	0.040	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	.;T;T;.;T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T;.;T;T;T;T
M_CAP	Benign	0.031	D
MetaRNN	Uncertain	0.49	T;T;T;T;T;T
MetaSVM	Uncertain	0.059	D
MutationAssessor	Benign	1.7	L;L;L;.;.;.
PrimateAI	Uncertain	0.79	T
PROVEAN	Benign	-1.7	N;N;N;N;.;.
REVEL	Uncertain	0.32
Sift	Benign	0.060	T;D;D;D;.;.
Sift4G	Uncertain	0.053	T;T;T;T;T;T
Polyphen		0.99, 0.98	.;D;D;D;.;.
Vest4		0.72
MutPred		0.28		Loss of ubiquitination at K272 (P = 0.0896);Loss of ubiquitination at K272 (P = 0.0896);Loss of ubiquitination at K272 (P = 0.0896);.;.;.;
MVP		0.83
MPC		0.24
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.24
gMVP		0.35

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: chr11-99827693;