Genetic Variant CERT1:c.*9+5134_*9+5138delTTTTT (chr5-75374198-GAAAAA-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001130105.1(CERT1):c.*10-12_*10-8delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0028 in 216,796 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 29)

Exomes 𝑓: 0.0028 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CERT1
NM_001130105.1 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.975

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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	HGVSc	Effect	Exon Rank	Protein	UniProt
CERT1	NM_001130105.1	c.10-12_10-8delTTTTT	splice_region intron	N/A	NP_001123577.1	Q9Y5P4-3
CERT1	NM_001379002.1	c.9+5134_9+5138delTTTTT	intron	N/A	NP_001365931.1	Q9Y5P4-1
CERT1	NM_005713.3	c.10-12_10-8delTTTTT	splice_region intron	N/A	NP_005704.1	Q9Y5P4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CERT1	ENST00000261415.12	TSL:1	c.9+5134_9+5138delTTTTT	intron	N/A	ENSP00000261415.8	Q9Y5P4-1
CERT1	ENST00000405807.10	TSL:5	c.10-12_10-8delTTTTT	splice_region intron	N/A	ENSP00000383996.4	Q9Y5P4-3
CERT1	ENST00000957920.1		c.10-12_10-8delTTTTT	splice_region intron	N/A	ENSP00000627979.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

84604

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD4 exome

AF:

0.00280

AC:

608

AN:

216796

Hom.:

AF XY:

0.00276

AC XY:

305

AN XY:

110460

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00238

AC:

AN:

6312

American (AMR)

AF:

0.00503

AC:

AN:

6558

Ashkenazi Jewish (ASJ)

AF:

0.00368

AC:

AN:

8150

East Asian (EAS)

AF:

0.00230

AC:

AN:

20432

South Asian (SAS)

AF:

0.00285

AC:

AN:

2454

European-Finnish (FIN)

AF:

0.00312

AC:

AN:

16966

Middle Eastern (MID)

AF:

0.00351

AC:

AN:

1138

European-Non Finnish (NFE)

AF:

0.00274

AC:

385

AN:

140414

Other (OTH)

AF:

0.00237

AC:

AN:

14372

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.249

Heterozygous variant carriers

176

263

351

439

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

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

84624

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

40008

African (AFR)

AF:

0.00

AC:

AN:

24524

American (AMR)

AF:

0.00

AC:

AN:

7256

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2136

East Asian (EAS)

AF:

0.00

AC:

AN:

3086

South Asian (SAS)

AF:

0.00

AC:

AN:

2640

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3708

Middle Eastern (MID)

AF:

0.00

AC:

AN:

128

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

39536

Other (OTH)

AF:

0.00

AC:

AN:

1104

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.97

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over