1-20652002-C-CTT

Position:

• chr1-20652002-C-CTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_005216.5(DDOST):​c.*376_*377insAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0306 in 159,134 control chromosomes in the GnomAD database, including 235 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.032 (234 hom., cov: 31)
  • Exomes 𝑓: 0.0025 (1 hom.)
• Consequence: DDOST NM_005216.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.147

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 -10 ACMG points.

• BP6: Variant 1-20652002-C-CTT is Benign according to our data. Variant chr1-20652002-C-CTT is described in ClinVar as [Likely_benign]. Clinvar id is 295050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0972 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDOST	NM_005216.5	c.*376_*377insAA		3_prime_UTR_variant	11/11	ENST00000602624.7	NP_005207.3
PINK1-AS	NR_046507.1	n.191_192insAA		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDOST	ENST00000602624.7	c.*376_*377insAA		3_prime_UTR_variant	11/11	1	NM_005216.5	ENSP00000473655	P1
DDOST	ENST00000415136.6	c.*376_*377insAA		3_prime_UTR_variant	11/11	1		ENSP00000399457
PINK1-AS	ENST00000451424.1	n.191_192insAA		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.0317 AC: 4808 AN: 151548 Hom.: 226 Cov.: 31

Gnomad AFR AF: 0.0993

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0130

Gnomad ASJ AF: 0.0113

Gnomad EAS AF: 0.0286

Gnomad SAS AF: 0.0454

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00100

Gnomad OTH AF: 0.0236

GnomAD4 exome AF: 0.00254 AC: 19 AN: 7468 Hom.: 1 Cov.: 0 AF XY: 0.00351 AC XY: 14 AN XY: 3984

Gnomad4 AFR exome AF: 0.0435

Gnomad4 AMR exome AF: 0.00204

Gnomad4 ASJ exome AF: 0.0132

Gnomad4 EAS exome AF: 0.0204

Gnomad4 SAS exome AF: 0.00921

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000206

Gnomad4 OTH exome AF: 0.00552

GnomAD4 genome AF: 0.0320 AC: 4856 AN: 151666 Hom.: 234 Cov.: 31 AF XY: 0.0318 AC XY: 2357 AN XY: 74100

Gnomad4 AFR AF: 0.0997

Gnomad4 AMR AF: 0.0129

Gnomad4 ASJ AF: 0.0113

Gnomad4 EAS AF: 0.0286

Gnomad4 SAS AF: 0.0456

Gnomad4 FIN AF: 0.000190

Gnomad4 NFE AF: 0.00100

Gnomad4 OTH AF: 0.0310

Alfa AF: 0.00537 Hom.: 3

Bravo AF: 0.0350

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital disorder of glycosylation Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs200971370; hg19: chr1-20978495;