1-20651801-TTTTATTTATTTA-T

Position:

• chr1-20651801-TTTTATTTATTTA-T

Variant summary

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

The NM_005216.5(DDOST):​c.*566_*577del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.4 in 147,092 control chromosomes in the GnomAD database, including 11,661 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.40 (11660 hom., cov: 0)
  • Exomes 𝑓: 0.38 (1 hom.)
• Consequence: DDOST NM_005216.5 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 0.131

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 1-20651801-TTTTATTTATTTA-T is Benign according to our data. Variant chr1-20651801-TTTTATTTATTTA-T is described in ClinVar as [Likely_benign]. Clinvar id is 295043.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.418 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDOST	NM_005216.5	c.*566_*577del		3_prime_UTR_variant	11/11	ENST00000602624.7	NP_005207.3
PINK1-AS	NR_046507.1	n.381_392del		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDOST	ENST00000602624.7	c.*566_*577del		3_prime_UTR_variant	11/11	1	NM_005216.5	ENSP00000473655	P1
DDOST	ENST00000415136.6	c.*566_*577del		3_prime_UTR_variant	11/11	1		ENSP00000399457
PINK1-AS	ENST00000451424.1	n.381_392del		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.400 AC: 58777 AN: 146994 Hom.: 11658 Cov.: 0

Gnomad AFR AF: 0.402

Gnomad AMI AF: 0.336

Gnomad AMR AF: 0.427

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.445

Gnomad NFE AF: 0.404

Gnomad OTH AF: 0.409

GnomAD4 exome AF: 0.375 AC: 3 AN: 8 Hom.: 1 AF XY: 0.375 AC XY: 3 AN XY: 8

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.400 AC: 58808 AN: 147084 Hom.: 11660 Cov.: 0 AF XY: 0.401 AC XY: 28654 AN XY: 71394

Gnomad4 AFR AF: 0.402

Gnomad4 AMR AF: 0.427

Gnomad4 ASJ AF: 0.428

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.315

Gnomad4 FIN AF: 0.410

Gnomad4 NFE AF: 0.404

Gnomad4 OTH AF: 0.407

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital disorder of glycosylation Benign:1

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: rs78039244; hg19: chr1-20978294;