rs143317974

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001130105.1(CERT1):c.310C>T(p.Pro104Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,578,656 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00057 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

CERT1
NM_001130105.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: 1.03

Publications

1 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 links:

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]

POLK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017495215).

BP6

Variant 5-75511282-G-A is Benign according to our data. Variant chr5-75511282-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 521299.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 87 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001130105.1. 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.-75C>T		5_prime_UTR	Exon 1 of 17	NP_001365958.1	Q9Y5P4-1
CERT1	NM_001130105.1		c.310C>T	p.Pro104Ser	missense	Exon 2 of 19	NP_001123577.1	Q9Y5P4-3
CERT1	NM_001379002.1		c.-75C>T		5_prime_UTR	Exon 1 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.-75C>T		5_prime_UTR	Exon 1 of 17	ENSP00000495760.1	Q9Y5P4-1
CERT1	ENST00000261415.12	TSL:1	c.-75C>T		5_prime_UTR	Exon 1 of 18	ENSP00000261415.8	Q9Y5P4-1
CERT1	ENST00000405807.10	TSL:5	c.310C>T	p.Pro104Ser	missense	Exon 2 of 19	ENSP00000383996.4	Q9Y5P4-3

Frequencies

GnomAD3 genomes

AF:

0.000558

AC:

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD2 exomes

AF:

0.000109

AC:

AN:

183036

AF XY:

0.0000800

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.000111

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000132

Gnomad OTH exome

AF:

0.000205

GnomAD4 exome

AF:

0.0000582

AC:

AN:

1426312

Hom.:

Cov.:

AF XY:

0.0000594

AC XY:

AN XY:

706652

show subpopulations

African (AFR)

AF:

0.00202

AC:

AN:

32736

American (AMR)

AF:

0.000156

AC:

AN:

38444

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25516

East Asian (EAS)

AF:

0.00

AC:

AN:

37706

South Asian (SAS)

AF:

0.00

AC:

AN:

82820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49974

Middle Eastern (MID)

AF:

0.000351

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.00000183

AC:

AN:

1094296

Other (OTH)

AF:

0.000118

AC:

AN:

59116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000571

AC:

AN:

152344

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.00197

AC:

AN:

41586

American (AMR)

AF:

0.000196

AC:

AN:

15310

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68022

Other (OTH)

AF:

0.000945

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000279

Hom.:

Bravo

AF:

0.000767

ExAC

AF:

0.0000933

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

CERT1-related disorder (1)

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.53

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.017

MetaSVM

Benign

-1.0

PhyloP100

1.0

PrimateAI

Uncertain

0.73

Polyphen

0.0

ClinPred

0.072

GERP RS

2.8

PromoterAI

-0.042

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

gMVP

0.39

Mutation Taster

=95/5

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over