Genetic Variant NRCAM:p.Ile1164Val (chr7-108160469-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001037132.4(NRCAM):c.3490A>G(p.Ile1164Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,092 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. I1164F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

NRCAM
NM_001037132.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.27

Publications

0 publications found

Variant links:

Genes affected

NRCAM (HGNC:7994): (neuronal cell adhesion molecule) Cell adhesion molecules (CAMs) are members of the immunoglobulin superfamily. This gene encodes a neuronal cell adhesion molecule with multiple immunoglobulin-like C2-type domains and fibronectin type-III domains. This ankyrin-binding protein is involved in neuron-neuron adhesion and promotes directional signaling during axonal cone growth. This gene is also expressed in non-neural tissues and may play a general role in cell-cell communication via signaling from its intracellular domain to the actin cytoskeleton during directional cell migration. Allelic variants of this gene have been associated with autism and addiction vulnerability. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

NRCAM Gene-Disease associations (from GenCC):

neurodevelopmental disorder with neuromuscular and skeletal abnormalities
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

NRCAM links:

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ACMG classification

Classification was made for transcript

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=0.22048983).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4 link	c.3490A>G	p.Ile1164Val	missense_variant	Exon 31 of 33	ENST00000379028.8	NP_001032209.1	Q92823-1Q14CA1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8 link	c.3490A>G	p.Ile1164Val	missense_variant	Exon 31 of 33	5	NM_001037132.4	ENSP00000368314.3		Q92823-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461092

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726802

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33448

American (AMR)

AF:

0.00

AC:

AN:

44644

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26112

East Asian (EAS)

AF:

0.00

AC:

AN:

39658

South Asian (SAS)

AF:

0.00

AC:

AN:

86092

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111620

Other (OTH)

AF:

0.00

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.036

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.31

T;.;.;.;.;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.94

D;D;D;D;D;.

M_CAP

Benign

0.015

MetaRNN

Benign

0.22

T;T;T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Uncertain

2.2

M;.;.;.;.;M

PhyloP100

6.3

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.89

N;.;N;N;.;N

REVEL

Benign

0.13

Sift

Pathogenic

0.0

D;.;D;D;.;D

Sift4G

Uncertain

0.0040

D;T;T;T;D;D

Polyphen

0.80

P;.;P;.;.;P

Vest4

0.20

MutPred

0.29

Loss of sheet (P = 0.1158);.;.;.;.;Loss of sheet (P = 0.1158);

MVP

0.75

MPC

0.80

ClinPred

0.95

GERP RS

5.5

Varity_R

0.37

gMVP

0.28

Mutation Taster

=75/25

polymorphism

(source)

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

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7-108160469-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over