rs372883632

Variant names:

• chr7-108149936-C-G
• rs372883632
• NM_001037132.4:c.3889G>C

Your query was ambiguous. Multiple possible variants found:

• chr7-108149936-C-G
• chr7-108149936-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001037132.4(NRCAM):​c.3889G>C​(p.Val1297Leu) variant causes a missense change. 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.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NRCAM NM_001037132.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.00

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.238817).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NRCAM	NM_001037132.4	c.3889G>C	p.Val1297Leu	missense_variant	Exon 33 of 33	ENST00000379028.8	NP_001032209.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NRCAM	ENST00000379028.8	c.3889G>C	p.Val1297Leu	missense_variant	Exon 33 of 33	5	NM_001037132.4	ENSP00000368314.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T;.;.;.;.;T
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.99	D;D;D;D;D;.
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.24	T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.80	N;.;.;.;.;N
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.0	N;.;N;N;.;N
REVEL	Benign	0.28
Sift	Benign	0.45	T;.;T;T;.;T
Sift4G	Benign	0.21	T;T;T;T;T;T
Polyphen		0.81	P;.;D;.;.;P
Vest4		0.29
MutPred		0.094		Gain of glycosylation at P1296 (P = 0.1376);.;.;.;.;Gain of glycosylation at P1296 (P = 0.1376);
MVP		0.67
MPC		0.85
ClinPred		0.76	D
GERP RS		6.2
Varity_R		0.28
gMVP		0.21

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: rs372883632; hg19: chr7-107790381;