5-75374136-CTTTT-CT

Variant names:

• chr5-75374136-CTTT-C
• rs545323650
• ENST00000261415.12:c.*9+5198_*9+5200delAAA

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001379004.1(CERT1):​c.1722_1724delAAA​(p.Lys575del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 138,498 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: 𝑓 0.000022 (0 hom., cov: 31)
• Consequence: CERT1 NM_001379004.1 disruptive_inframe_deletion
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_001379004.1. Strenght limited to Supporting due to length of the change: 1aa.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CERT1	NM_001379004.1	c.1722_1724delAAA	p.Lys575del	disruptive_inframe_deletion	Exon 16 of 16		NP_001365933.1
CERT1	XM_011543090.4	c.1800_1802delAAA	p.Lys601del	disruptive_inframe_deletion	Exon 17 of 17		XP_011541392.1
CERT1	NM_001130105.1	c.*62_*64delAAA		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+5198_*9+5200delAAA		intron_variant	Intron 17 of 17	1		ENSP00000261415.8
CERT1	ENST00000642556.1	c.1722_1724delAAA	p.Lys575del	disruptive_inframe_deletion	Exon 16 of 16			ENSP00000496016.1
CERT1	ENST00000644072	c.*62_*64delAAA		3_prime_UTR_variant	Exon 18 of 18			ENSP00000494110.2

Frequencies

GnomAD3 genomes AF: 0.0000217 AC: 3 AN: 138498 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000803

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

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0000217 AC: 3 AN: 138498 Hom.: 0 Cov.: 31 AF XY: 0.0000300 AC XY: 2 AN XY: 66616

Gnomad4 AFR AF: 0.0000803

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

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;