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. Variant got 4 ACMG points: 4P and 0B. PVS1_Moderate 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

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0534 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERT1	NM_001379004.1	c.1721_1724delAAAA	p.Lys574SerfsTer2	frameshift_variant	Exon 16 of 16		NP_001365933.1
CERT1	XM_011543090.4	c.1799_1802delAAAA	p.Lys600SerfsTer2	frameshift_variant	Exon 17 of 17		XP_011541392.1
CERT1	NM_001130105.1	c.*61_*64delAAAA		3_prime_UTR_variant	Exon 19 of 19		NP_001123577.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CERT1	ENST00000261415.12	c.*9+5197_*9+5200delAAAA		intron_variant	Intron 17 of 17	1		ENSP00000261415.8
CERT1	ENST00000642556.1	c.1721_1724delAAAA	p.Lys574SerfsTer2	frameshift_variant	Exon 16 of 16			ENSP00000496016.1
CERT1	ENST00000644072	c.*61_*64delAAAA		3_prime_UTR_variant	Exon 18 of 18			ENSP00000494110.2

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

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: 0.00000751

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs545323650; hg19: chr5-74669961;