10-77975715-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_007055.4(POLR3A):c.*1763G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,228 control chromosomes in the GnomAD database, including 2,095 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.16 (2094 hom., cov: 32)
  • Exomes 𝑓: 0.12 (1 hom.)
• Consequence: POLR3A NM_007055.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.05

Genes affected

POLR3A (HGNC:30074): (RNA polymerase III subunit A) The protein encoded by this gene is the catalytic component of RNA polymerase III, which synthesizes small RNAs. The encoded protein also acts as a sensor to detect foreign DNA and trigger an innate immune response. [provided by RefSeq, Aug 2011]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 10-77975715-C-T is Benign according to our data. Variant chr10-77975715-C-T is described in ClinVar as [Benign]. Clinvar id is 300999.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR3A	NM_007055.4	c.*1763G>A		3_prime_UTR_variant	31/31	ENST00000372371.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLR3A	ENST00000372371.8	c.*1763G>A		3_prime_UTR_variant	31/31	1	NM_007055.4	P1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24334 AN: 152044 Hom.: 2096 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.339

Gnomad AMR AF: 0.150

Gnomad ASJ AF: 0.208

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.172

Gnomad OTH AF: 0.174

GnomAD4 exome AF: 0.121 AC: 8 AN: 66 Hom.: 1 Cov.: 0 AF XY: 0.125 AC XY: 7 AN XY: 56

Gnomad4 ASJ exome AF: 0.00

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.107

GnomAD4 genome AF: 0.160 AC: 24338 AN: 152162 Hom.: 2094 Cov.: 32 AF XY: 0.158 AC XY: 11770 AN XY: 74392

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.150

Gnomad4 ASJ AF: 0.208

Gnomad4 EAS AF: 0.274

Gnomad4 SAS AF: 0.148

Gnomad4 FIN AF: 0.147

Gnomad4 NFE AF: 0.172

Gnomad4 OTH AF: 0.172

Alfa AF: 0.171 Hom.: 4599

Bravo AF: 0.162

Asia WGS AF: 0.197 AC: 683 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leukoencephalopathy-ataxia-hypodontia-hypomyelination syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.098
Dann	Benign	0.61
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs4979935; hg19: chr10-79735473;