rs968182062

Variant names:

• chr1-11934788-C-A
• rs968182062
• NM_000302.4:c.9C>A

Your query was ambiguous. Multiple possible variants found:

• chr1-11934788-C-A
• chr1-11934788-C-G
• chr1-11934788-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_000302.4(PLOD1):​c.9C>A​(p.Pro3Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000721 in 1,387,030 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P3P) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: PLOD1 NM_000302.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0720
• 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Orphanet, PanelApp Australia, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.27).
• BP7: Synonymous conserved (PhyloP=0.072 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PLOD1	NM_000302.4	c.9C>A	p.Pro3Pro	synonymous_variant	Exon 1 of 19	ENST00000196061.5	NP_000293.2
PLOD1	NM_001316320.2	c.9C>A	p.Pro3Pro	synonymous_variant	Exon 1 of 20		NP_001303249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PLOD1	ENST00000196061.5	c.9C>A	p.Pro3Pro	synonymous_variant	Exon 1 of 19	1	NM_000302.4	ENSP00000196061.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.21e-7 AC: 1 AN: 1387030 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 684506

African (AFR) AF: 0.00 AC: 0 AN: 31014

American (AMR) AF: 0.00 AC: 0 AN: 35582

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25034

East Asian (EAS) AF: 0.00 AC: 0 AN: 35386

South Asian (SAS) AF: 0.00 AC: 0 AN: 78766

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40666

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5118

European-Non Finnish (NFE) AF: 9.28e-7 AC: 1 AN: 1077742

Other (OTH) AF: 0.00 AC: 0 AN: 57722

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.27
CADD	Benign	8.8
DANN	Benign	0.88
PhyloP100		0.072
PromoterAI		-0.0041	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8
Mutation Taster		=100/0	polymorphism

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: rs968182062; hg19: chr1-11994845;