1-20651917-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005216.5(DDOST):c.*462A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.43 in 154,560 control chromosomes in the GnomAD database, including 14,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (14285 hom., cov: 31)
  • Exomes 𝑓: 0.37 (218 hom.)
• Consequence: DDOST NM_005216.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.12

Genes affected

DDOST (HGNC:2728): (dolichyl-diphosphooligosaccharide--protein glycosyltransferase non-catalytic subunit) This gene encodes a component of the oligosaccharyltransferase complex which catalyzes the transfer of high-mannose oligosaccharides to asparagine residues on nascent polypeptides in the lumen of the rough endoplasmic reticulum. The protein complex co-purifies with ribosomes. The product of this gene is also implicated in the processing of advanced glycation endproducts (AGEs), which form from non-enzymatic reactions between sugars and proteins or lipids and are associated with aging and hyperglycemia. [provided by RefSeq, Jul 2008]

PINK1-AS (HGNC:38872): (PINK1 antisense RNA)

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-20651917-T-C is Benign according to our data. Variant chr1-20651917-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 295047.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.502 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DDOST	NM_005216.5	c.*462A>G		3_prime_UTR_variant	11/11	ENST00000602624.7
PINK1-AS	NR_046507.1	n.277A>G		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DDOST	ENST00000602624.7	c.*462A>G		3_prime_UTR_variant	11/11	1	NM_005216.5	P1
DDOST	ENST00000415136.6	c.*462A>G		3_prime_UTR_variant	11/11	1
PINK1-AS	ENST00000451424.1	n.277A>G		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65340 AN: 151718 Hom.: 14259 Cov.: 31

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.331

Gnomad AMR AF: 0.438

Gnomad ASJ AF: 0.441

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.403

Gnomad OTH AF: 0.430

GnomAD4 exome AF: 0.369 AC: 1006 AN: 2724 Hom.: 218 Cov.: 0 AF XY: 0.371 AC XY: 528 AN XY: 1422

Gnomad4 AFR exome AF: 0.313

Gnomad4 AMR exome AF: 0.398

Gnomad4 ASJ exome AF: 0.389

Gnomad4 EAS exome AF: 0.227

Gnomad4 SAS exome AF: 0.357

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.372

Gnomad4 OTH exome AF: 0.365

GnomAD4 genome AF: 0.431 AC: 65421 AN: 151836 Hom.: 14285 Cov.: 31 AF XY: 0.431 AC XY: 32005 AN XY: 74204

Gnomad4 AFR AF: 0.508

Gnomad4 AMR AF: 0.438

Gnomad4 ASJ AF: 0.441

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.394

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.434

Alfa AF: 0.415 Hom.: 1602

Bravo AF: 0.436

Asia WGS AF: 0.383 AC: 1332 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Parkinson Disease, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.6
Dann	Benign	0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs559542; hg19: chr1-20978410;