rs1043895

chr7-108184520-C-G

Variant summary

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

The NM_001037132.4(NRCAM):c.2130G>C(p.Lys710Asn) 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NRCAM NM_001037132.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.248

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=0.22014612).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NRCAM	NM_001037132.4	c.2130G>C	p.Lys710Asn	missense_variant	21/33	ENST00000379028.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NRCAM	ENST00000379028.8	c.2130G>C	p.Lys710Asn	missense_variant	21/33	5	NM_001037132.4	P1
NRCAM	ENST00000379024.8	c.2073G>C	p.Lys691Asn	missense_variant	20/30	1
NRCAM	ENST00000351718.8	c.2082G>C	p.Lys694Asn	missense_variant	19/28	1
NRCAM	ENST00000413765.6	c.2130G>C	p.Lys710Asn	missense_variant	21/31	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	21
Dann	Uncertain	0.99
DEOGEN2	Benign	0.23	T;.;.;.;.;T;.
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.45
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;.;D
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.22	T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.18	N;.;.;.;.;N;.
MutationTaster	Benign	0.99	D;D;D;D;D;D
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.8	N;N;N;N;.;N;.
REVEL	Benign	0.029
Sift	Benign	0.065	T;T;T;T;.;T;.
Sift4G	Benign	0.11	T;T;T;T;T;T;T
Polyphen		0.024	B;.;B;.;.;B;.
Vest4		0.11
MutPred		0.43		Loss of ubiquitination at K710 (P = 0.021);Loss of ubiquitination at K710 (P = 0.021);.;.;.;Loss of ubiquitination at K710 (P = 0.021);.;
MVP		0.60
MPC		0.28
ClinPred		0.53	D
GERP RS		-0.53
Varity_R		0.097
gMVP		0.45

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: rs1043895; hg19: chr7-107824964;