Genetic Variant CERCAM:p.Phe231Ile (chr9-128424539-T-A) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_016174.5(CERCAM):c.691T>A(p.Phe231Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000246 in 1,461,846 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F231L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

CERCAM
NM_016174.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.01

Publications

0 publications found

Variant links:

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]

CERCAM links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.921

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.691T>A	p.Phe231Ile	missense	Exon 5 of 13	NP_057258.3
	CERCAM	NM_001286760.1		c.457T>A	p.Phe153Ile	missense	Exon 5 of 13	NP_001273689.1	Q5T4B2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CERCAM	ENST00000372838.9	TSL:1 MANE Select	c.691T>A	p.Phe231Ile	missense	Exon 5 of 13	ENSP00000361929.4	Q5T4B2-1
CERCAM	ENST00000463535.5	TSL:1	n.367T>A		non_coding_transcript_exon	Exon 2 of 8
CERCAM	ENST00000951772.1		c.763T>A	p.Phe255Ile	missense	Exon 5 of 13	ENSP00000621831.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251420

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000246

AC:

AN:

1461846

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727234

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000306

AC:

AN:

1112008

Other (OTH)

AF:

0.0000166

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000189

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.68

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.40

MetaRNN

Pathogenic

0.92

MetaSVM

Uncertain

0.69

MutationAssessor

Uncertain

2.9

PhyloP100

8.0

PrimateAI

Uncertain

0.72

PROVEAN

Pathogenic

-5.2

REVEL

Pathogenic

0.88

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.89

MVP

0.94

MPC

0.67

ClinPred

0.99

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.79

gMVP

0.97

Mutation Taster

=54/46

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over