10-77975616-C-T

Position:

• chr10-77975616-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.*1862G>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 0.0405 in 152,454 control chromosomes in the GnomAD database, including 295 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.041 (294 hom., cov: 32)
  • Exomes 𝑓: 0.038 (1 hom.)
• Consequence: POLR3A NM_007055.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.732

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=-0.79).
• BP6: Variant 10-77975616-C-T is Benign according to our data. Variant chr10-77975616-C-T is described in ClinVar as [Benign]. Clinvar id is 300994.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
POLR3A	NM_007055.4	c.*1862G>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.*1862G>A		3_prime_UTR_variant	31/31	1	NM_007055.4	P1

Frequencies

GnomAD3 genomes AF: 0.0405 AC: 6170 AN: 152232 Hom.: 295 Cov.: 32

Gnomad AFR AF: 0.0202

Gnomad AMI AF: 0.0384

Gnomad AMR AF: 0.0838

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0309

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0246

Gnomad OTH AF: 0.0440

GnomAD4 exome AF: 0.0385 AC: 4 AN: 104 Hom.: 1 Cov.: 0 AF XY: 0.0147 AC XY: 1 AN XY: 68

Gnomad4 AFR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0385

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.375

GnomAD4 genome AF: 0.0405 AC: 6177 AN: 152350 Hom.: 294 Cov.: 32 AF XY: 0.0454 AC XY: 3380 AN XY: 74512

Gnomad4 AFR AF: 0.0201

Gnomad4 AMR AF: 0.0842

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.225

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.0309

Gnomad4 NFE AF: 0.0246

Gnomad4 OTH AF: 0.0478

Alfa AF: 0.0294 Hom.: 13

Bravo AF: 0.0414

Asia WGS AF: 0.205 AC: 712 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	-0.79
CADD	Benign	2.5
DANN	Benign	0.85

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: rs12572507; hg19: chr10-79735374;