11-100061278-A-C

Variant names:

• chr11-100061278-A-C
• NM_014361.4:c.1047A>C
• CNTN5 p.Lys349Asn

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014361.4(CNTN5):​c.1047A>C​(p.Lys349Asn) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: CNTN5 NM_014361.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.661
• 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]

LOC105369456 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3928807).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014361.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN5	NM_014361.4	MANE Select	c.1047A>C	p.Lys349Asn	missense	Exon 10 of 25	NP_055176.1	O94779-1
	CNTN5	NM_001243270.2		c.1047A>C	p.Lys349Asn	missense	Exon 9 of 24	NP_001230199.1	O94779-1
	CNTN5	NM_175566.2		c.825A>C	p.Lys275Asn	missense	Exon 7 of 22	NP_780775.1	O94779-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CNTN5	ENST00000524871.6	TSL:1 MANE Select	c.1047A>C	p.Lys349Asn	missense	Exon 10 of 25	ENSP00000435637.1	O94779-1
	CNTN5	ENST00000418526.6	TSL:1	c.825A>C	p.Lys275Asn	missense	Exon 7 of 22	ENSP00000393229.2	O94779-2
	CNTN5	ENST00000527185.5	TSL:1	c.1047A>C	p.Lys349Asn	missense	Exon 10 of 21	ENSP00000433575.1	O94779-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.19	T
Eigen	Benign	0.10
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-0.65	T
MutationAssessor	Benign	-0.20	N
PhyloP100		0.66
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.45
Sift	Benign	0.11	T
Sift4G	Benign	0.15	T
Varity_R		0.19
gMVP		0.58
Mutation Taster		=84/16	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-99932010;