rs3176150

Variant names:

• chr15-89335343-T-C
• rs3176150
• ENST00000562356.1:n.73T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000562356.1(POLG-DT):​n.73T>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 ENST00000562356.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.117
• Publications: 2 publications found

Genes affected

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

TRR-TCG1-1 (HGNC:34827):

ACMG classification

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLG-DT	NR_186332.1	n.525T>C		non_coding_transcript_exon_variant	Exon 2 of 2
TRR-TCG1-1	unassigned_transcript_2746	c.*198T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLG-DT	ENST00000562356.1	n.73T>C		non_coding_transcript_exon_variant	Exon 1 of 2	3
POLG-DT	ENST00000569473.1	n.291T>C		non_coding_transcript_exon_variant	Exon 1 of 1	6
POLG-DT	ENST00000837147.1	n.429T>C		non_coding_transcript_exon_variant	Exon 2 of 2

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

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 4

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

African (AFR) AF: 0.000506 AC: 21 AN: 41512

American (AMR) AF: 0.00137 AC: 21 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0211 AC: 73 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5148

South Asian (SAS) AF: 0.0193 AC: 93 AN: 4822

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00438 AC: 298 AN: 67996

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

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
PhyloP100		0.12
PromoterAI		-0.0039	Neutral

Splicing

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

Other links and lift over

dbSNP: rs3176150; hg19: chr15-89878574;