rs1748354

Variant names:

• chr10-26704461-T-A
• rs1748354
• NM_014317.5:c.163-216T>A

Your query was ambiguous. Multiple possible variants found:

• chr10-26704461-T-A
• chr10-26704461-T-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014317.5(PDSS1):​c.163-216T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.522 in 151,968 control chromosomes in the GnomAD database, including 21,799 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.52 (21799 hom., cov: 32)
• Consequence: PDSS1 NM_014317.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.147
• Publications: 3 publications found

Genes affected

PDSS1 (HGNC:17759): (decaprenyl diphosphate synthase subunit 1) The protein encoded by this gene is an enzyme that elongates the prenyl side-chain of coenzyme Q, or ubiquinone, one of the key elements in the respiratory chain. The gene product catalyzes the formation of all trans-polyprenyl pyrophosphates from isopentyl diphosphate in the assembly of polyisoprenoid side chains, the first step in coenzyme Q biosynthesis. The protein may be peripherally associated with the inner mitochondrial membrane, though no transit peptide has been definitively identified to date. Defects in this gene are a cause of coenzyme Q10 deficiency. [provided by RefSeq, Jul 2008]

PDSS1 Gene-Disease associations (from GenCC):

• deafness-encephaloneuropathy-obesity-valvulopathy syndrome

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-26704461-T-A is Benign according to our data. Variant chr10-26704461-T-A is described in ClinVar as Benign. ClinVar VariationId is 683440.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.606 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PDSS1	NM_014317.5	c.163-216T>A		intron_variant	Intron 2 of 11	ENST00000376215.10	NP_055132.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PDSS1	ENST00000376215.10	c.163-216T>A		intron_variant	Intron 2 of 11	1	NM_014317.5	ENSP00000365388.5

Frequencies

GnomAD3 genomes AF: 0.523 AC: 79361 AN: 151850 Hom.: 21800 Cov.: 32

Gnomad AFR AF: 0.358

Gnomad AMI AF: 0.583

Gnomad AMR AF: 0.616

Gnomad ASJ AF: 0.586

Gnomad EAS AF: 0.420

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.596

Gnomad OTH AF: 0.550

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.522 AC: 79381 AN: 151968 Hom.: 21799 Cov.: 32 AF XY: 0.521 AC XY: 38721 AN XY: 74260

African (AFR) AF: 0.358 AC: 14842 AN: 41462

American (AMR) AF: 0.616 AC: 9407 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.586 AC: 2035 AN: 3470

East Asian (EAS) AF: 0.421 AC: 2172 AN: 5164

South Asian (SAS) AF: 0.376 AC: 1810 AN: 4808

European-Finnish (FIN) AF: 0.640 AC: 6733 AN: 10528

Middle Eastern (MID) AF: 0.633 AC: 186 AN: 294

European-Non Finnish (NFE) AF: 0.596 AC: 40515 AN: 67958

Other (OTH) AF: 0.547 AC: 1153 AN: 2106

Alfa AF: 0.554 Hom.: 2963

Bravo AF: 0.516

Asia WGS AF: 0.374 AC: 1298 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	9.2
DANN	Benign	0.78
PhyloP100		0.15
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1748354; hg19: chr10-26993390;