12-106363847-ATTC-A

Position:

• chr12-106363847-ATTC-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_018082.6(POLR3B):​c.73-17_73-15del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00286 in 1,594,216 control chromosomes in the GnomAD database, including 111 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (59 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (52 hom.)
• Consequence: POLR3B NM_018082.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.536

Genes affected

POLR3B (HGNC:30348): (RNA polymerase III subunit B) This gene encodes the second largest subunit of RNA polymerase III, the polymerase responsible for synthesizing transfer and small ribosomal RNAs in eukaryotes. The largest subunit and the encoded protein form the catalytic center of RNA polymerase III. Mutations in this gene are a cause of hypomyelinating leukodystrophy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-106363847-ATTC-A is Benign according to our data. Variant chr12-106363847-ATTC-A is described in ClinVar as [Benign]. Clinvar id is 1168762.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR3B	NM_018082.6	c.73-17_73-15del		intron_variant		ENST00000228347.9
POLR3B	NM_001160708.2	c.-102-17_-102-15del		intron_variant
POLR3B	XM_017019621.3	c.73-17_73-15del		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR3B	ENST00000228347.9	c.73-17_73-15del		intron_variant		1	NM_018082.6	P1
POLR3B	ENST00000539066.5	c.-102-17_-102-15del		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0155 AC: 2356 AN: 152200 Hom.: 59 Cov.: 32

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000413

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00392 AC: 984 AN: 250790 Hom.: 27 AF XY: 0.00296 AC XY: 401 AN XY: 135482

Gnomad AFR exome AF: 0.0545

Gnomad AMR exome AF: 0.00212

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000198

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000881

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00152 AC: 2192 AN: 1441898 Hom.: 52 AF XY: 0.00131 AC XY: 940 AN XY: 718616

Gnomad4 AFR exome AF: 0.0548

Gnomad4 AMR exome AF: 0.00242

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.000129

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000384

Gnomad4 OTH exome AF: 0.00353

GnomAD4 genome AF: 0.0155 AC: 2366 AN: 152318 Hom.: 59 Cov.: 32 AF XY: 0.0147 AC XY: 1097 AN XY: 74498

Gnomad4 AFR AF: 0.0541

Gnomad4 AMR AF: 0.00588

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00855 Hom.: 7

Bravo AF: 0.0178

Asia WGS AF: 0.00289 AC: 10 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs140678013; hg19: chr12-106757625;