11-99819697-T-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_014361.4(CNTN5):c.209T>G(p.Leu70Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.49 (0 hom., cov: 54)
  • Exomes 𝑓: 0.48 (5 hom.)
  • Failed GnomAD Quality Control
• Consequence: CNTN5 NM_014361.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.847

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 Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0017924607).
• BP6: Variant 11-99819697-T-G is Benign according to our data. Variant chr11-99819697-T-G is described in ClinVar as [Benign]. Clinvar id is 768471.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CNTN5	NM_014361.4	c.209T>G	p.Leu70Arg	missense_variant	4/25	ENST00000524871.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CNTN5	ENST00000524871.6	c.209T>G	p.Leu70Arg	missense_variant	4/25	1	NM_014361.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 72605 AN: 149464 Hom.: 0 Cov.: 54 FAILED QC

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.500

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.407

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.485

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.495

Gnomad OTH AF: 0.489

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.485 AC: 643618 AN: 1328178 Hom.: 5 Cov.: 70 AF XY: 0.485 AC XY: 322173 AN XY: 664450

Gnomad4 AFR exome AF: 0.484

Gnomad4 AMR exome AF: 0.448

Gnomad4 ASJ exome AF: 0.496

Gnomad4 EAS exome AF: 0.388

Gnomad4 SAS exome AF: 0.473

Gnomad4 FIN exome AF: 0.484

Gnomad4 NFE exome AF: 0.490

Gnomad4 OTH exome AF: 0.485

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.486 AC: 72654 AN: 149574 Hom.: 0 Cov.: 54 AF XY: 0.484 AC XY: 35340 AN XY: 73004

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.406

Gnomad4 SAS AF: 0.471

Gnomad4 FIN AF: 0.485

Gnomad4 NFE AF: 0.495

Gnomad4 OTH AF: 0.488

Alfa AF: 0.186 Hom.: 13

ExAC AF: 0.475 AC: 57043

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 14, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
Cadd	Benign	13
Dann	Benign	0.21
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.084	N
LIST_S2	Benign	0.20	T;.;T;T
MetaRNN	Benign	0.0018	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.8	N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P;P
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.39	N;N;N;.
REVEL	Benign	0.12
Sift	Benign	1.0	T;T;T;.
Sift4G	Benign	0.35	T;T;T;T
Polyphen		0.0	.;B;B;.
Vest4		0.20
MPC		0.045
ClinPred		0.0041	T
GERP RS		3.1
Varity_R		0.055
gMVP		0.31

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

LitVar

Other links and lift over

dbSNP: rs7125822; hg19: chr11-99690428; COSMIC: COSV54277807;