Variant chr9-128428768-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_016174.5(CERCAM):c.898C>T(p.Arg300Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000121 in 1,613,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

CERCAM
NM_016174.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59

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]

CERCAM links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34267208).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CERCAM	NM_016174.5 linkuse as main transcript	c.898C>T	p.Arg300Cys	missense_variant	7/13	ENST00000372838.9	NP_057258.3
CERCAM	NM_001286760.1 linkuse as main transcript	c.664C>T	p.Arg222Cys	missense_variant	7/13		NP_001273689.1
CERCAM	XM_011518763.4 linkuse as main transcript	c.664C>T	p.Arg222Cys	missense_variant	7/13		XP_011517065.1
CERCAM	XM_047423450.1 linkuse as main transcript	c.664C>T	p.Arg222Cys	missense_variant	8/14		XP_047279406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERCAM	ENST00000372838.9 linkuse as main transcript	c.898C>T	p.Arg300Cys	missense_variant	7/13	1	NM_016174.5	ENSP00000361929	P1	Q5T4B2-1

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000478

AC:

AN:

251272

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135878

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000880

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000127

AC:

186

AN:

1461754

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

727188

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000592

AC:

AN:

152032

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74272

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000642

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 09, 2024

The c.898C>T (p.R300C) alteration is located in exon 7 (coding exon 7) of the CERCAM gene. This alteration results from a C to T substitution at nucleotide position 898, causing the arginine (R) at amino acid position 300 to be replaced by a cysteine (C). 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

0.12

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0032

.;T;T

Eigen

Benign

0.13

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.81

T;T;T

M_CAP

Benign

0.081

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

0.0

.;N;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.99

N;N;.

REVEL

Uncertain

0.35

Sift

Uncertain

0.0060

D;D;.

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

0.72

.;P;.

Vest4

0.38

MVP

0.78

MPC

0.33

ClinPred

0.29

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.82

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over