Genetic Variant CCER1:p.Glu351Gln (chr12-90953692-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152638.4(CCER1):c.1051G>C(p.Glu351Gln) 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 1,461,726 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

CCER1
NM_152638.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.780

Variant links:

Genes affected

CCER1 (HGNC:28373): (coiled-coil glutamate rich protein 1)

CCER1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09708947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCER1	NM_152638.4 link	c.1051G>C	p.Glu351Gln	missense_variant	Exon 1 of 1	ENST00000358859.3	NP_689851.1	Q8TC90
CCER1	NR_130711.2 link	n.55-773G>C		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCER1	ENST00000358859.3 link	c.1051G>C	p.Glu351Gln	missense_variant	Exon 1 of 1	6	NM_152638.4	ENSP00000351727.2	Q8TC90
CCER1	ENST00000549707.1 link	n.4G>C		non_coding_transcript_exon_variant	Exon 1 of 2	3		ENSP00000446773.1	H0YHB9
CCER1	ENST00000548187.1 link	n.53-773G>C		intron_variant	Intron 1 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251438

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135890

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461726

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727176

show subpopulations

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:

0.00000450

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000164

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 12, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1051G>C (p.E351Q) alteration is located in exon 1 (coding exon 1) of the CCER1 gene. This alteration results from a G to C substitution at nucleotide position 1051, causing the glutamic acid (E) at amino acid position 351 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.61

CADD

Benign

1.8

DANN

Benign

0.45

DEOGEN2

Benign

0.014

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.27

M_CAP

Benign

0.0055

MetaRNN

Benign

0.097

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PrimateAI

Benign

0.30

PROVEAN

Benign

-1.1

REVEL

Benign

0.15

Sift

Benign

0.50

Sift4G

Uncertain

0.010

Polyphen

0.92

Vest4

0.067

MutPred

0.11

Gain of helix (P = 0.0225);

MVP

0.17

MPC

0.29

ClinPred

0.15

GERP RS

3.2

Varity_R

0.050

gMVP

0.027

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over