rs761359367

Variant names:

• chr9-128422951-T-C
• NM_016174.5:c.281T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-128422951-T-C
• chr9-128422951-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_016174.5(CERCAM):​c.281T>C​(p.Val94Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,596 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CERCAM NM_016174.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.05

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.824

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERCAM	NM_016174.5	c.281T>C	p.Val94Ala	missense_variant	Exon 2 of 13	ENST00000372838.9	NP_057258.3
CERCAM	NM_001286760.1	c.47T>C	p.Val16Ala	missense_variant	Exon 2 of 13		NP_001273689.1
CERCAM	XM_011518763.4	c.47T>C	p.Val16Ala	missense_variant	Exon 2 of 13		XP_011517065.1
CERCAM	XM_047423450.1	c.47T>C	p.Val16Ala	missense_variant	Exon 3 of 14		XP_047279406.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERCAM	ENST00000372838.9	c.281T>C	p.Val94Ala	missense_variant	Exon 2 of 13	1	NM_016174.5	ENSP00000361929.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461596 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727116

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.23
BayesDel_addAF	Pathogenic	0.37	D
BayesDel_noAF	Pathogenic	0.30
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.18	.;.;T;.;T;.;T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.74	T;T;T;T;T;T;T
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.82	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.67	D
MutationAssessor	Pathogenic	2.9	.;.;.;.;M;.;.
PrimateAI	Uncertain	0.55	T
PROVEAN	Uncertain	-3.8	D;D;D;D;D;D;.
REVEL	Pathogenic	0.84
Sift	Uncertain	0.0010	D;D;D;D;D;D;.
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		1.0	.;.;.;.;D;.;.
Vest4		0.33, 0.57, 0.57
MutPred		0.42		.;.;.;.;Loss of sheet (P = 0.0817);.;.;
MVP		0.96
MPC		0.60
ClinPred		1.0	D
GERP RS		4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.47
gMVP		0.81

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr9-131185230;