chr7-101209892-T-C

Variant names:

• chr7-101209892-T-C
• rs1468358
• NM_001084.5:c.1683+201A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001084.5(PLOD3):​c.1683+201A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.348 in 574,578 control chromosomes in the GnomAD database, including 37,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12371 hom., cov: 32)
  • Exomes 𝑓: 0.33 (25092 hom.)
• Consequence: PLOD3 NM_001084.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.814
• Publications: 17 publications found

Genes affected

PLOD3 (HGNC:9083): (procollagen-lysine,2-oxoglutarate 5-dioxygenase 3) The protein encoded by this gene is a membrane-bound homodimeric enzyme that is localized to the cisternae of the rough 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 VIB have deficiencies in lysyl hydroxylase activity. [provided by RefSeq, Jul 2008]

PLOD3 Gene-Disease associations (from GenCC):

• bone fragility with contractures, arterial rupture, and deafness

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 7-101209892-T-C is Benign according to our data. Variant chr7-101209892-T-C is described in ClinVar as Benign. ClinVar VariationId is 1251775.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001084.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLOD3	NM_001084.5	MANE Select	c.1683+201A>G		intron	N/A	NP_001075.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PLOD3	ENST00000223127.8	TSL:1 MANE Select	c.1683+201A>G		intron	N/A	ENSP00000223127.3
	PLOD3	ENST00000460132.5	TSL:3	n.508A>G		non_coding_transcript_exon	Exon 3 of 3
	PLOD3	ENST00000454310.5	TSL:5	c.405+201A>G		intron	N/A	ENSP00000407555.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58502 AN: 151972 Hom.: 12342 Cov.: 32

Gnomad AFR AF: 0.562

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.251

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.388

GnomAD4 exome AF: 0.334 AC: 141099 AN: 422488 Hom.: 25092 Cov.: 0 AF XY: 0.339 AC XY: 74776 AN XY: 220794

African (AFR) AF: 0.557 AC: 6740 AN: 12098

American (AMR) AF: 0.284 AC: 4717 AN: 16632

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 5038 AN: 13240

East Asian (EAS) AF: 0.462 AC: 13906 AN: 30106

South Asian (SAS) AF: 0.442 AC: 17273 AN: 39036

European-Finnish (FIN) AF: 0.255 AC: 7300 AN: 28676

Middle Eastern (MID) AF: 0.356 AC: 682 AN: 1916

European-Non Finnish (NFE) AF: 0.300 AC: 76796 AN: 256022

Other (OTH) AF: 0.349 AC: 8647 AN: 24762

GnomAD4 genome AF: 0.385 AC: 58589 AN: 152090 Hom.: 12371 Cov.: 32 AF XY: 0.381 AC XY: 28316 AN XY: 74318

African (AFR) AF: 0.563 AC: 23361 AN: 41500

American (AMR) AF: 0.310 AC: 4727 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 1330 AN: 3470

East Asian (EAS) AF: 0.480 AC: 2473 AN: 5156

South Asian (SAS) AF: 0.449 AC: 2161 AN: 4812

European-Finnish (FIN) AF: 0.251 AC: 2655 AN: 10586

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20683 AN: 67980

Other (OTH) AF: 0.385 AC: 814 AN: 2114

Alfa AF: 0.318 Hom.: 14176

Bravo AF: 0.393

Asia WGS AF: 0.457 AC: 1589 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Sep 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.75
DANN	Benign	0.48
PhyloP100		-0.81
Mutation Taster		=100/0	polymorphism (auto)

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: rs1468358; hg19: chr7-100853173;