NM_016174.5:c.338A>G

Variant names:

• chr9-128423175-A-G
• rs1833751500
• NM_016174.5:c.338A>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016174.5(CERCAM):​c.338A>G​(p.His113Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,818 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: CERCAM NM_016174.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.32
• 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: Uncertain_significance. The variant received 2 ACMG points.

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

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.338A>G	p.His113Arg	missense	Exon 3 of 13	NP_057258.3
	CERCAM	NM_001286760.1		c.104A>G	p.His35Arg	missense	Exon 3 of 13	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.338A>G	p.His113Arg	missense	Exon 3 of 13	ENSP00000361929.4	Q5T4B2-1
	CERCAM	ENST00000951772.1		c.338A>G	p.His113Arg	missense	Exon 3 of 13	ENSP00000621831.1
	CERCAM	ENST00000951773.1		c.338A>G	p.His113Arg	missense	Exon 3 of 13	ENSP00000621832.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461818 Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3 AN XY: 727224

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111994

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 32

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	0.33
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Benign	-0.090
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.68
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.060	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Uncertain	0.18	D
MutationAssessor	Uncertain	2.7	M
PhyloP100		9.3
PrimateAI	Uncertain	0.61	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Uncertain	0.61
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.026	D
Polyphen		0.83	P
Vest4		0.36
MutPred		0.32		Gain of solvent accessibility (P = 0.0704)
MVP		0.93
MPC		0.56
ClinPred		0.99	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.62
gMVP		0.76
Mutation Taster		=58/42	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

dbSNP: rs1833751500; hg19: chr9-131185454;