Genetic Variant NM_001379029.1:c.1823G>C (chr5-75379398-C-G) – 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_001379029.1(CERT1):c.1823G>C(p.Arg608Pro) 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 not provided (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R608C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

CERT1
NM_001379029.1 missense

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 6.17

Publications

0 publications found

Variant links:

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 Gene-Disease associations (from GenCC):

intellectual disability, autosomal dominant 34
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

CERT1 links:

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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, 0.891

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379029.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CERT1	NM_001379029.1	MANE Select	c.1823G>C	p.Arg608Pro	missense	Exon 17 of 17	NP_001365958.1	Q9Y5P4-1
CERT1	NM_001130105.1		c.2207G>C	p.Arg736Pro	missense	Exon 18 of 19	NP_001123577.1	Q9Y5P4-3
CERT1	NM_001379002.1		c.1823G>C	p.Arg608Pro	missense	Exon 17 of 18	NP_001365931.1	Q9Y5P4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CERT1	ENST00000643780.2	MANE Select	c.1823G>C	p.Arg608Pro	missense	Exon 17 of 17	ENSP00000495760.1	Q9Y5P4-1
CERT1	ENST00000261415.12	TSL:1	c.1823G>C	p.Arg608Pro	missense	Exon 17 of 18	ENSP00000261415.8	Q9Y5P4-1
CERT1	ENST00000405807.10	TSL:5	c.2207G>C	p.Arg736Pro	missense	Exon 18 of 19	ENSP00000383996.4	Q9Y5P4-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:not provided

Revision:no classification provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

COL4A3BP-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Pathogenic

0.39

BayesDel_noAF

Pathogenic

0.33

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.77

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.97

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.89

MetaSVM

Uncertain

0.31

MutationAssessor

Uncertain

2.4

PhyloP100

6.2

PrimateAI

Pathogenic

0.85

PROVEAN

Pathogenic

-5.5

REVEL

Pathogenic

0.78

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0070

Polyphen

1.0

Vest4

0.94

MutPred

0.66

Loss of MoRF binding (P = 5e-04)

MVP

0.95

ClinPred

1.0

GERP RS

4.8

Varity_R

0.95

gMVP

0.98

Mutation Taster

=15/85

disease causing

(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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over