chr9-128423242-C-G

Variant names:

• chr9-128423242-C-G
• rs139357437
• NM_016174.5:c.405C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016174.5(CERCAM):​c.405C>G​(p.Asn135Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,650 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: CERCAM NM_016174.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.095403135).

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.405C>G	p.Asn135Lys	missense	Exon 3 of 13	NP_057258.3
	CERCAM	NM_001286760.1		c.171C>G	p.Asn57Lys	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.405C>G	p.Asn135Lys	missense	Exon 3 of 13	ENSP00000361929.4	Q5T4B2-1
	CERCAM	ENST00000951772.1		c.405C>G	p.Asn135Lys	missense	Exon 3 of 13	ENSP00000621831.1
	CERCAM	ENST00000951773.1		c.405C>G	p.Asn135Lys	missense	Exon 3 of 13	ENSP00000621832.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000342 AC: 5 AN: 1461650 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727140

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

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

European-Non Finnish (NFE) AF: 0.00000450 AC: 5 AN: 1111916

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

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.40
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.036	D
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Benign	-1.4	N
PhyloP100		0.35
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.040	N
REVEL	Benign	0.20
Sift	Benign	0.47	T
Sift4G	Uncertain	0.037	D
Polyphen		0.0	B
Vest4		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
Mutation Taster		=91/9	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: rs139357437; hg19: chr9-131185521;