ENST00000569473.1:n.108T>C

Variant names:

• chr15-89335160-T-C
• rs2856268
• ENST00000569473.1:n.108T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (9456 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: POLG-DT ENST00000569473.1 non_coding_transcript_exon
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -7.58
• Publications: 18 publications found

Genes affected

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

TRR-TCG1-1 (HGNC:34827):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 15-89335160-T-C is Benign according to our data. Variant chr15-89335160-T-C is described in ClinVar as Benign. ClinVar VariationId is 695736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.393 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000569473.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLG-DT	NR_186332.1		n.369-27T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLG-DT	ENST00000569473.1	TSL:6	n.108T>C		non_coding_transcript_exon	Exon 1 of 1
	POLG-DT	ENST00000837150.1		n.118T>C		non_coding_transcript_exon	Exon 1 of 2
	POLG-DT	ENST00000837151.1		n.117T>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.339 AC: 51608 AN: 152022 Hom.: 9451 Cov.: 32

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: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 1 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.339 AC: 51622 AN: 152140 Hom.: 9456 Cov.: 32 AF XY: 0.346 AC XY: 25756 AN XY: 74368

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: 96 AN: 294

European-Non Finnish (NFE) AF: 0.397 AC: 26962 AN: 67982

Other (OTH) AF: 0.331 AC: 699 AN: 2110

Alfa AF: 0.242 Hom.: 771

Bravo AF: 0.326

Asia WGS AF: 0.340 AC: 1181 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Progressive sclerosing poliodystrophy (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.0020
DANN	Benign	0.47
PhyloP100		-7.6
PromoterAI		0.033	Neutral
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

Other links and lift over

dbSNP: rs2856268; hg19: chr15-89878391;