12-90954070-C-T

Variant names:

• chr12-90954070-C-T
• rs1876561745
• NM_152638.4:c.673G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152638.4(CCER1):​c.673G>A​(p.Ala225Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 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)
• Consequence: CCER1 NM_152638.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.149
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.060182184).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152638.4. 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
	CCER1	NM_152638.4	MANE Select	c.673G>A	p.Ala225Thr	missense	Exon 1 of 1	NP_689851.1	Q8TC90
	CCER1	NR_130711.2		n.54+1053G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCER1	ENST00000358859.3	TSL:6 MANE Select	c.673G>A	p.Ala225Thr	missense	Exon 1 of 1	ENSP00000351727.2	Q8TC90
	CCER1	ENST00000548187.1	TSL:3	n.52+1053G>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	0.079
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	10
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0041	T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.91
FATHMM_MKL	Benign	0.096	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N
PhyloP100		-0.15
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.48	N
REVEL	Benign	0.0030
Sift	Benign	0.30	T
Sift4G	Benign	0.19	T
Polyphen		0.29	B
Vest4		0.034
MutPred		0.16		Gain of catalytic residue at R229 (P = 0.0155)
MVP		0.16
MPC		0.90
ClinPred		0.11	T
GERP RS		2.1
Varity_R		0.022
gMVP		0.051
Mutation Taster		=100/0	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: rs1876561745; hg19: chr12-91347847;