rs182113726

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001037132.4(NRCAM):c.3259G>A(p.Glu1087Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000472 in 1,609,912 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00049 ( 2 hom. )

Consequence

NRCAM
NM_001037132.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.907

Publications

4 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:

LOC102724363 (HGNC:):

LOC102724363 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.050746173).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037132.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NRCAM	NM_001037132.4	MANE Select	c.3259G>A	p.Glu1087Lys	missense	Exon 29 of 33	NP_001032209.1	Q92823-1
NRCAM	NM_001371156.1		c.3268G>A	p.Glu1090Lys	missense	Exon 29 of 33	NP_001358085.1
NRCAM	NM_001371131.1		c.3259G>A	p.Glu1087Lys	missense	Exon 30 of 34	NP_001358060.1	Q92823-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NRCAM	ENST00000379028.8	TSL:5 MANE Select	c.3259G>A	p.Glu1087Lys	missense	Exon 29 of 33	ENSP00000368314.3	Q92823-1
NRCAM	ENST00000379024.8	TSL:1	c.3130+6991G>A		intron	N/A	ENSP00000368310.4	Q92823-6
NRCAM	ENST00000351718.8	TSL:1	c.3104-7839G>A		intron	N/A	ENSP00000325269.6	Q92823-4

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000321

AC:

AN:

245816

AF XY:

0.000367

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.000181

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000481

Gnomad OTH exome

AF:

0.000849

GnomAD4 exome

AF:

0.000488

AC:

711

AN:

1457648

Hom.:

Cov.:

AF XY:

0.000490

AC XY:

355

AN XY:

724974

show subpopulations

African (AFR)

AF:

0.000150

AC:

AN:

33332

American (AMR)

AF:

0.000159

AC:

AN:

44026

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26082

East Asian (EAS)

AF:

0.00

AC:

AN:

39486

South Asian (SAS)

AF:

0.000422

AC:

AN:

85244

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53338

Middle Eastern (MID)

AF:

0.000694

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000568

AC:

631

AN:

1110158

Other (OTH)

AF:

0.000432

AC:

AN:

60222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

107

142

178

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000322

AC:

AN:

152264

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41556

American (AMR)

AF:

0.0000654

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000541

Hom.:

Bravo

AF:

0.000261

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000485

AC:

ExAC

AF:

0.000364

AC:

EpiCase

AF:

0.000824

EpiControl

AF:

0.00102

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.32

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.16

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.34

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.042

MetaRNN

Benign

0.051

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

0.91

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.82

REVEL

Benign

0.088

Sift

Benign

0.63

Sift4G

Benign

0.88

Polyphen

0.030

Vest4

0.18

MVP

0.61

MPC

0.27

ClinPred

0.020

GERP RS

1.8

Varity_R

0.056

gMVP

0.57

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over