7-101209892-T-C

Position:

• chr7-101209892-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PLOD3	NM_001084.5	c.1683+201A>G		intron_variant		ENST00000223127.8	NP_001075.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PLOD3	ENST00000223127.8	c.1683+201A>G		intron_variant		1	NM_001084.5	ENSP00000223127	P1
PLOD3	ENST00000454310.5	c.407+201A>G		intron_variant		5		ENSP00000407555
PLOD3	ENST00000460132.5	n.508A>G		non_coding_transcript_exon_variant	3/3	3
PLOD3	ENST00000487563.1	n.347+201A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR exome AF: 0.557

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.381

Gnomad4 EAS exome AF: 0.462

Gnomad4 SAS exome AF: 0.442

Gnomad4 FIN exome AF: 0.255

Gnomad4 NFE exome AF: 0.300

Gnomad4 OTH exome AF: 0.349

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

Gnomad4 AFR AF: 0.563

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.480

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.251

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.385

Alfa AF: 0.310 Hom.: 9827

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.75
DANN	Benign	0.48

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: rs1468358; hg19: chr7-100853173;