chr1-20651917-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.12
Variant links:
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)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 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_multiple_submitters_no_conflicts, 2 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 Protein UniProt
DDOSTNM_005216.5 linkuse as main transcriptc.*462A>G 3_prime_UTR_variant 11/11 ENST00000602624.7 NP_005207.3
PINK1-ASNR_046507.1 linkuse as main transcriptn.277A>G non_coding_transcript_exon_variant 1/3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DDOSTENST00000602624.7 linkuse as main transcriptc.*462A>G 3_prime_UTR_variant 11/111 NM_005216.5 ENSP00000473655 P1
DDOSTENST00000415136.6 linkuse as main transcriptc.*462A>G 3_prime_UTR_variant 11/111 ENSP00000399457 P39656-1
PINK1-ASENST00000451424.1 linkuse as main transcriptn.277A>G non_coding_transcript_exon_variant 1/32

Frequencies

GnomAD3 genomes
AF:
0.431
AC:
65340
AN:
151718
Hom.:
14259
Cov.:
31
show subpopulations
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
show subpopulations
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
show subpopulations
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:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Parkinson Disease, Recessive Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs559542; hg19: chr1-20978410; API