PLOD1 p.Ala544Ala

Variant names:

• chr1-11966295-G-G
• NM_000302.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr1-11966296--
• chr1-11966298-A-T
• chr1-11966298-A-C
• chr1-11966298-A-G

Variant summary

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

The NM_000302.4(PLOD1):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 28)
• Consequence: PLOD1 NM_000302.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.56
• Publications: 0 publications found

Genes affected

PLOD1 (HGNC:9081): (procollagen-lysine,2-oxoglutarate 5-dioxygenase 1) Lysyl hydroxylase is a membrane-bound homodimeric protein localized to the cisternae of the endoplasmic reticulum. The enzyme (cofactors iron and ascorbate) catalyzes the hydroxylation of lysyl residues in collagen-like peptides. The resultant hydroxylysyl groups are attachment sites for carbohydrates in collagen and thus are critical for the stability of intermolecular crosslinks. Some patients with Ehlers-Danlos syndrome type VI have deficiencies in lysyl hydroxylase activity. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2015]

PLOD1 Gene-Disease associations (from GenCC):

• Ehlers-Danlos syndrome, kyphoscoliotic type 1

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, G2P, Orphanet, 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_000302.4. 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
	PLOD1	NM_000302.4	MANE Select	c.		exon_region	Exon 12 of 19	NP_000293.2
	PLOD1	NM_001316320.2		c.		exon_region	Exon 13 of 20	NP_001303249.1	Q02809-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLOD1	ENST00000196061.5	TSL:1 MANE Select	c.		intron	N/A	ENSP00000196061.4	Q02809-1
	PLOD1	ENST00000854019.1		c.		intron	N/A	ENSP00000524078.1
	PLOD1	ENST00000854031.1		c.		intron	N/A	ENSP00000524090.1

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 28

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-12026352;