1-20651801-T-TTTTTTTTATTTATTTATTTA

Position:

• chr1-20651801-T-TTTTTTTTATTTATTTATTTA

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_Supporting BS2

The NM_005216.5(DDOST):​c.*577_*578insTAAATAAATAAATAAAAAAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0091 (16 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DDOST NM_005216.5 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.118

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 Likely_benign. Variant got -5 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00906 (1334/147160) while in subpopulation EAS AF= 0.0369 (182/4936). AF 95% confidence interval is 0.0325. There are 16 homozygotes in gnomad4. There are 695 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
• BS2: High Homozygotes in GnomAd4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DDOST	NM_005216.5	c.*577_*578insTAAATAAATAAATAAAAAAA		3_prime_UTR_variant	11/11	ENST00000602624.7	NP_005207.3
PINK1-AS	NR_046507.1	n.392_393insTAAATAAATAAATAAAAAAA		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DDOST	ENST00000602624.7	c.*577_*578insTAAATAAATAAATAAAAAAA		3_prime_UTR_variant	11/11	1	NM_005216.5	ENSP00000473655	P1
DDOST	ENST00000415136.6	c.*577_*578insTAAATAAATAAATAAAAAAA		3_prime_UTR_variant	11/11	1		ENSP00000399457
PINK1-AS	ENST00000451424.1	n.392_393insTAAATAAATAAATAAAAAAA		non_coding_transcript_exon_variant	1/3	2

Frequencies

GnomAD3 genomes AF: 0.00906 AC: 1332 AN: 147070 Hom.: 16 Cov.: 0

Gnomad AFR AF: 0.00436

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0160

Gnomad ASJ AF: 0.00232

Gnomad EAS AF: 0.0368

Gnomad SAS AF: 0.0310

Gnomad FIN AF: 0.0188

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.00600

Gnomad OTH AF: 0.00642

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 8

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00906 AC: 1334 AN: 147160 Hom.: 16 Cov.: 0 AF XY: 0.00973 AC XY: 695 AN XY: 71434

Gnomad4 AFR AF: 0.00435

Gnomad4 AMR AF: 0.0161

Gnomad4 ASJ AF: 0.00232

Gnomad4 EAS AF: 0.0369

Gnomad4 SAS AF: 0.0310

Gnomad4 FIN AF: 0.0188

Gnomad4 NFE AF: 0.00600

Gnomad4 OTH AF: 0.00686

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital disorder of glycosylation Uncertain:1

Uncertain significance, 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: rs886045853; hg19: chr1-20978294;