rs983472984

Variant names:

• chr9-128420930-C-A
• rs983472984
• NM_016174.5:c.53C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-128420930-C-A
• chr9-128420930-C-G
• chr9-128420930-C-T

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.53C>A​(p.Pro18Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000155 in 1,286,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. P18L) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: CERCAM NM_016174.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.65
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.074927986).

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.53C>A	p.Pro18Gln	missense	Exon 1 of 13	NP_057258.3
	CERCAM	NM_001286760.1		c.-38+1652C>A		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.53C>A	p.Pro18Gln	missense	Exon 1 of 13	ENSP00000361929.4	Q5T4B2-1
	CERCAM	ENST00000951772.1		c.53C>A	p.Pro18Gln	missense	Exon 1 of 13	ENSP00000621831.1
	CERCAM	ENST00000951773.1		c.53C>A	p.Pro18Gln	missense	Exon 1 of 13	ENSP00000621832.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000155 AC: 2 AN: 1286926 Hom.: 0 Cov.: 31 AF XY: 0.00000158 AC XY: 1 AN XY: 633940

African (AFR) AF: 0.00 AC: 0 AN: 26382

American (AMR) AF: 0.00 AC: 0 AN: 22540

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22386

East Asian (EAS) AF: 0.00 AC: 0 AN: 27822

South Asian (SAS) AF: 0.00 AC: 0 AN: 67600

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4984

European-Non Finnish (NFE) AF: 0.00000194 AC: 2 AN: 1029540

Other (OTH) AF: 0.00 AC: 0 AN: 52768

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	8.8
DANN	Benign	0.82
DEOGEN2	Benign	0.00021	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.060	N
LIST_S2	Benign	0.37	T
M_CAP	Pathogenic	0.66	D
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.7
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.29	N
REVEL	Benign	0.13
Sift	Benign	0.32	T
Sift4G	Benign	0.35	T
Polyphen		0.0030	B
Vest4		0.083
MutPred		0.37		Loss of loop (P = 9e-04)
MVP		0.10
MPC		0.12
ClinPred		0.12	T
GERP RS		-2.5
PromoterAI		-0.12	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.035
gMVP		0.55
Mutation Taster		=96/4	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: rs983472984; hg19: chr9-131183209;