5-75379398-C-A

Position:

• chr5-75379398-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001379029.1(CERT1):​c.1823G>T​(p.Arg608Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CERT1 NM_001379029.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.17

Genes affected

CERT1 (HGNC:2205): (ceramide transporter 1) This gene encodes a kinase that specifically phosphorylates the N-terminal region of the non-collagenous domain of the alpha 3 chain of type IV collagen, known as the Goodpasture antigen. Goodpasture disease is the result of an autoimmune response directed at this antigen. One isoform of this protein is also involved in ceramide intracellular transport. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

CERT1 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.88

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CERT1	NM_001379029.1	c.1823G>T	p.Arg608Leu	missense_variant	17/17	ENST00000643780.2	NP_001365958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CERT1	ENST00000643780.2	c.1823G>T	p.Arg608Leu	missense_variant	17/17		NM_001379029.1	ENSP00000495760.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Nov 06, 2019

Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Pathogenic	0.39	D
BayesDel_noAF	Pathogenic	0.32
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.67	.;.;D;.;.;.;.;D;D;.;.
Eigen	Uncertain	0.63
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Pathogenic	0.98	.;D;.;.;D;D;.;.;D;D;D
M_CAP	Uncertain	0.15	D
MetaRNN	Pathogenic	0.88	D;D;D;D;D;D;D;D;D;D;D
MetaSVM	Uncertain	0.15	D
MutationAssessor	Uncertain	2.4	.;.;M;.;.;.;.;M;M;.;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-5.7	.;.;.;.;.;.;.;D;.;.;.
REVEL	Pathogenic	0.80
Sift	Uncertain	0.0020	.;.;.;.;.;.;.;D;.;.;.
Sift4G	Uncertain	0.0090	.;.;.;.;.;.;.;D;.;.;.
Polyphen		0.99	D;D;D;.;.;.;D;D;D;.;D
Vest4		0.95
MutPred		0.62		.;.;Loss of MoRF binding (P = 0.0045);.;.;.;.;Loss of MoRF binding (P = 0.0045);Loss of MoRF binding (P = 0.0045);.;.;
MVP		0.97
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.73
gMVP		0.93

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr5-74675223;