9-128423242-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016174.5(CERCAM):​c.405C>A​(p.Asn135Lys) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

CERCAM
NM_016174.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.349
Variant links:
Genes affected
CERCAM (HGNC:23723): (cerebral endothelial cell adhesion molecule) Enables identical protein binding activity. Acts upstream of or within cell adhesion. Predicted to be located in endoplasmic reticulum lumen. [provided by Alliance of Genome Resources, Apr 2022]

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ACMG classification

Classification made for transcript

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=0.10055444).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CERCAMNM_016174.5 linkc.405C>A p.Asn135Lys missense_variant Exon 3 of 13 ENST00000372838.9 NP_057258.3 Q5T4B2-1
CERCAMNM_001286760.1 linkc.171C>A p.Asn57Lys missense_variant Exon 3 of 13 NP_001273689.1 Q5T4B2-2
CERCAMXM_011518763.4 linkc.171C>A p.Asn57Lys missense_variant Exon 3 of 13 XP_011517065.1 Q5T4B2-2
CERCAMXM_047423450.1 linkc.171C>A p.Asn57Lys missense_variant Exon 4 of 14 XP_047279406.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CERCAMENST00000372838.9 linkc.405C>A p.Asn135Lys missense_variant Exon 3 of 13 1 NM_016174.5 ENSP00000361929.4 Q5T4B2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 02, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.405C>A (p.N135K) alteration is located in exon 3 (coding exon 3) of the CERCAM gene. This alteration results from a C to A substitution at nucleotide position 405, causing the asparagine (N) at amino acid position 135 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.082
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
15
DANN
Benign
0.96
DEOGEN2
Benign
0.0038
.;.;T;.;T;.;T
Eigen
Benign
-0.58
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.54
T;T;T;T;T;T;T
M_CAP
Benign
0.041
D
MetaRNN
Benign
0.10
T;T;T;T;T;T;T
MetaSVM
Benign
-0.76
T
MutationAssessor
Benign
-1.4
.;.;.;.;N;.;.
PrimateAI
Benign
0.33
T
PROVEAN
Benign
0.040
N;N;N;N;N;N;.
REVEL
Benign
0.20
Sift
Benign
0.47
T;T;T;T;T;T;.
Sift4G
Uncertain
0.037
D;T;T;T;T;T;T
Polyphen
0.0
.;.;.;.;B;.;.
Vest4
0.14, 0.14, 0.14
MutPred
0.57
.;.;.;.;Gain of methylation at N135 (P = 0.0186);.;.;
MVP
0.63
MPC
0.15
ClinPred
0.15
T
GERP RS
2.9
Varity_R
0.043
gMVP
0.37

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs139357437; hg19: chr9-131185521; API