rs3176150

Positions:

• chr15-89335343-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000569473.1(POLG-DT):​n.291T>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 0.00341 in 152,170 control chromosomes in the GnomAD database, including 5 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 0.0034 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POLG-DT ENST00000569473.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00341 (519/152170) while in subpopulation SAS AF= 0.0193 (93/4822). AF 95% confidence interval is 0.0161. There are 5 homozygotes in gnomad4. There are 258 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLG-DT	ENST00000569473.1	n.291T>C		non_coding_transcript_exon_variant	1/1
POLG-DT	ENST00000562356.1	n.73T>C		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes AF: 0.00341 AC: 519 AN: 152052 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.0211

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0191

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00438

Gnomad OTH AF: 0.00335

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 8 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00341 AC: 519 AN: 152170 Hom.: 5 Cov.: 32 AF XY: 0.00347 AC XY: 258 AN XY: 74406

Gnomad4 AFR AF: 0.000506

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.0211

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0193

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.00438

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00318 Hom.: 0

Bravo AF: 0.00329

Asia WGS AF: 0.00664 AC: 23 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	5.0
DANN	Benign	0.60

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3176150; hg19: chr15-89878574;