rs545323650

Variant names:

• chr5-75374136-CTTTT-C
• rs545323650
• ENST00000261415.12:c.*9+5197_*9+5200delAAAA

Your query was ambiguous. Multiple possible variants found:

• chr5-75374136-CTTTT-C
• chr5-75374136-CTTTT-CT
• chr5-75374136-CTTTT-CTT
• chr5-75374136-CTTTT-CTTT
• chr5-75374136-CTTTT-CTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001379004.1(CERT1):​c.1721_1724delAAAA​(p.Lys574SerfsTer2) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 207,516 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: CERT1 NM_001379004.1 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 0 publications found

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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001379004.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERT1	NM_001379004.1		c.1721_1724delAAAA	p.Lys574SerfsTer2	frameshift	Exon 16 of 16	NP_001365933.1	A0A2R8Y7C5
	CERT1	NM_001130105.1		c.*61_*64delAAAA		3_prime_UTR	Exon 19 of 19	NP_001123577.1	Q9Y5P4-3
	CERT1	NM_005713.3		c.*61_*64delAAAA		3_prime_UTR	Exon 18 of 18	NP_005704.1	Q9Y5P4-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CERT1	ENST00000261415.12	TSL:1	c.*9+5197_*9+5200delAAAA		intron	N/A	ENSP00000261415.8	Q9Y5P4-1
	CERT1	ENST00000642556.1		c.1721_1724delAAAA	p.Lys574SerfsTer2	frameshift	Exon 16 of 16	ENSP00000496016.1	A0A2R8Y7C5
	CERT1	ENST00000863487.1		c.*61_*64delAAAA		splice_region	Exon 17 of 17	ENSP00000533546.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000482 AC: 1 AN: 207516 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 105484

African (AFR) AF: 0.00 AC: 0 AN: 5900

American (AMR) AF: 0.00 AC: 0 AN: 6292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7670

East Asian (EAS) AF: 0.00 AC: 0 AN: 19332

South Asian (SAS) AF: 0.00 AC: 0 AN: 2790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 17652

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1100

European-Non Finnish (NFE) AF: 0.00000751 AC: 1 AN: 133118

Other (OTH) AF: 0.00 AC: 0 AN: 13662

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.3

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

Other links and lift over

dbSNP: rs545323650; hg19: chr5-74669961;