chr9-128420963-C-T

Variant names:

• chr9-128420963-C-T
• rs1041231675
• NM_016174.5:c.86C>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.86C>T​(p.Pro29Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000682 in 1,465,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P29S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: CERCAM NM_016174.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0410
• 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=0.21651918).

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.86C>T	p.Pro29Leu	missense	Exon 1 of 13	NP_057258.3
	CERCAM	NM_001286760.1		c.-38+1685C>T		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.86C>T	p.Pro29Leu	missense	Exon 1 of 13	ENSP00000361929.4	Q5T4B2-1
	CERCAM	ENST00000372842.5	TSL:5	c.-1942C>T		5_prime_UTR_premature_start_codon_gain	Exon 3 of 14	ENSP00000361933.1	Q5T4B2-2
	CERCAM	ENST00000411852.5	TSL:5	c.-457C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000403766.1	B7ZBS9

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152176 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000965

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000457 AC: 6 AN: 1313790 Hom.: 0 Cov.: 31 AF XY: 0.00000463 AC XY: 3 AN XY: 648112

African (AFR) AF: 0.00 AC: 0 AN: 27024

American (AMR) AF: 0.00 AC: 0 AN: 25826

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23276

East Asian (EAS) AF: 0.00 AC: 0 AN: 28150

South Asian (SAS) AF: 0.0000139 AC: 1 AN: 71708

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35034

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5292

European-Non Finnish (NFE) AF: 0.00000479 AC: 5 AN: 1043382

Other (OTH) AF: 0.00 AC: 0 AN: 54098

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152176 Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4 AN XY: 74332

African (AFR) AF: 0.0000965 AC: 4 AN: 41462

American (AMR) AF: 0.00 AC: 0 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000378

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	0.091
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.012	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.26
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.68	T
M_CAP	Pathogenic	0.82	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.041
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.23
Sift	Benign	0.046	D
Sift4G	Uncertain	0.024	D
Polyphen		0.0	B
Vest4		0.078
MutPred		0.47		Loss of glycosylation at P29 (P = 0.0631)
MVP		0.58
MPC		0.13
ClinPred		0.49	T
GERP RS		4.1
PromoterAI		-0.010	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.092
gMVP		0.42
Mutation Taster		=293/7	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: rs1041231675; hg19: chr9-131183242;