rs5744539

Variant summary

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

The NM_001130105.1(CERT1):​c.301G>C​(p.Asp101His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,414,350 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. D101N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 7.1e-7 ( 0 hom. )

Consequence

CERT1
NM_001130105.1 missense

Scores

3
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.04
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]
POLK (HGNC:9183): (DNA polymerase kappa) This gene encodes a member of the DNA polymerase type-Y family of proteins. The encoded protein is a specialized DNA polymerase that catalyzes translesion DNA synthesis, which allows DNA replication in the presence of DNA lesions. Human cell lines lacking a functional copy of this gene exhibit impaired genome integrity and enhanced susceptibility to oxidative damage. Mutations in this gene that impair enzyme activity may be associated with prostate cancer in human patients. [provided by RefSeq, Sep 2016]

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=0.22603852).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CERT1NM_001379029.1 linkc.-84G>C 5_prime_UTR_variant Exon 1 of 17 ENST00000643780.2 NP_001365958.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CERT1ENST00000643780.2 linkc.-84G>C 5_prime_UTR_variant Exon 1 of 17 NM_001379029.1 ENSP00000495760.1 Q9Y5P4-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
7.07e-7
AC:
1
AN:
1414350
Hom.:
0
Cov.:
32
AF XY:
0.00000143
AC XY:
1
AN XY:
699562
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:
9.19e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
19
DANN
Uncertain
0.99
Eigen
Benign
0.057
Eigen_PC
Benign
0.092
FATHMM_MKL
Benign
0.54
D
LIST_S2
Benign
0.51
T
M_CAP
Uncertain
0.18
D
MetaRNN
Benign
0.23
T
MetaSVM
Benign
-1.1
T
PrimateAI
Uncertain
0.77
T
Polyphen
0.43
B
MutPred
0.15
Gain of methylation at R105 (P = 0.0638);
ClinPred
0.97
D
GERP RS
3.7
gMVP
0.46

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-74807116; API