9-128428412-G-C

Position:

• chr9-128428412-G-C

Variant summary

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

The NM_016174.5(CERCAM):​c.877G>C​(p.Glu293Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CERCAM NM_016174.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.05

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERCAM	NM_016174.5	c.877G>C	p.Glu293Gln	missense_variant	6/13	ENST00000372838.9	NP_057258.3
CERCAM	NM_001286760.1	c.643G>C	p.Glu215Gln	missense_variant	6/13		NP_001273689.1
CERCAM	XM_011518763.4	c.643G>C	p.Glu215Gln	missense_variant	6/13		XP_011517065.1
CERCAM	XM_047423450.1	c.643G>C	p.Glu215Gln	missense_variant	7/14		XP_047279406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERCAM	ENST00000372838.9	c.877G>C	p.Glu293Gln	missense_variant	6/13	1	NM_016174.5	ENSP00000361929	P1

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

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 20, 2023

The c.877G>C (p.E293Q) alteration is located in exon 6 (coding exon 6) of the CERCAM gene. This alteration results from a G to C substitution at nucleotide position 877, causing the glutamic acid (E) at amino acid position 293 to be replaced by a glutamine (Q). 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	0.30
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.097	.;.;T;T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.82	T;T;T;T
M_CAP	Benign	0.043	D
MetaRNN	Uncertain	0.66	D;D;D;D
MetaSVM	Uncertain	-0.10	T
MutationAssessor	Benign	1.9	.;.;L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-2.5	N;D;D;.
REVEL	Uncertain	0.49
Sift	Uncertain	0.020	D;D;D;.
Sift4G	Uncertain	0.010	D;D;D;D
Polyphen		0.10	.;.;B;.
Vest4		0.31
MutPred		0.53		.;.;Gain of helix (P = 0.1736);.;
MVP		0.83
MPC		0.15
ClinPred		0.97	D
GERP RS		4.6
Varity_R		0.48
gMVP		0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-131190691;