Genetic Variant POLG-DT:n.108T>C (chr15-89335160-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000569473.1(POLG-DT):n.108T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.339 in 152,144 control chromosomes in the GnomAD database, including 9,456 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 9456 hom., cov: 32)

Exomes 𝑓: 0.25 ( 0 hom. )

Consequence

POLG-DT
ENST00000569473.1 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -7.58

Publications

18 publications found

Variant links:

Genes affected

POLG-DT (HGNC:55363): (POLG divergent transcript)

POLG-DT links:

TRR-TCG1-1 (HGNC:34827):

TRR-TCG1-1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLG-DT	NR_186332.1 link	n.369-27T>C		intron_variant	Intron 1 of 1
TRR-TCG1-1	unassigned_transcript_2746	c.*15T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL
POLG-DT	ENST00000569473.1 link	n.108T>C	non_coding_transcript_exon_variant	Exon 1 of 1	6
POLG-DT	ENST00000837150.1 link	n.118T>C	non_coding_transcript_exon_variant	Exon 1 of 2
POLG-DT	ENST00000837151.1 link	n.117T>C	non_coding_transcript_exon_variant	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.339

AC:

51608

AN:

152022

Hom.:

9451

Cov.:

show subpopulations

Gnomad AFR

AF:

0.204

Gnomad AMI

AF:

0.378

Gnomad AMR

AF:

0.333

Gnomad ASJ

AF:

0.359

Gnomad EAS

AF:

0.335

Gnomad SAS

AF:

0.394

Gnomad FIN

AF:

0.480

Gnomad MID

AF:

0.329

Gnomad NFE

AF:

0.397

Gnomad OTH

AF:

0.334

GnomAD4 exome

AF:

0.250

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.250

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.339

AC:

51622

AN:

152140

Hom.:

9456

Cov.:

AF XY:

0.346

AC XY:

25756

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.204

AC:

8485

AN:

41514

American (AMR)

AF:

0.332

AC:

5079

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.359

AC:

1246

AN:

3472

East Asian (EAS)

AF:

0.335

AC:

1735

AN:

5172

South Asian (SAS)

AF:

0.395

AC:

1902

AN:

4816

European-Finnish (FIN)

AF:

0.480

AC:

5074

AN:

10578

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.397

AC:

26962

AN:

67982

Other (OTH)

AF:

0.331

AC:

699

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1744

3488

5231

6975

8719

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.242

Hom.:

771

Bravo

AF:

0.326

Asia WGS

AF:

0.340

AC:

1181

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Oct 03, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 22684821) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Progressive sclerosing poliodystrophy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

0.0020

(source)

DANN

Benign

0.47

PhyloP100

-7.6

PromoterAI

0.033

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

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

Publications

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15-89335160-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over