NM_016174.5:c.128A>C

Variant names:

• chr9-128421005-A-C
• NM_016174.5:c.128A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016174.5(CERCAM):​c.128A>C​(p.Glu43Ala) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CERCAM NM_016174.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.172
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042598814).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016174.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERCAM	NM_016174.5	MANE Select	c.128A>C	p.Glu43Ala	missense	Exon 1 of 13	NP_057258.3
	CERCAM	NM_001286760.1		c.-38+1727A>C		intron	N/A	NP_001273689.1	Q5T4B2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERCAM	ENST00000372838.9	TSL:1 MANE Select	c.128A>C	p.Glu43Ala	missense	Exon 1 of 13	ENSP00000361929.4	Q5T4B2-1
	CERCAM	ENST00000951772.1		c.128A>C	p.Glu43Ala	missense	Exon 1 of 13	ENSP00000621831.1
	CERCAM	ENST00000951773.1		c.128A>C	p.Glu43Ala	missense	Exon 1 of 13	ENSP00000621832.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.098
BayesDel_addAF	Benign	-0.076	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	18
DANN	Benign	0.78
DEOGEN2	Benign	0.00088	T
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.78	T
M_CAP	Uncertain	0.28	D
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	-0.96	N
PhyloP100		0.17
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	1.9	N
REVEL	Benign	0.17
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0020	B
Vest4		0.073
MutPred		0.39		Loss of stability (P = 0.0465)
MVP		0.46
MPC		0.14
ClinPred		0.11	T
GERP RS		1.8
PromoterAI		-0.071	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.062
gMVP		0.71
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

hg19: chr9-131183284;