Variant chr10-77975616-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.732

Variant links:

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]

POLR3A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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 linkuse as main transcript	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 linkuse as main transcript	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.:

show subpopulations

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:

AN:

104

Hom.:

Cov.:

AF XY:

0.0147

AC XY:

AN XY:

show subpopulations

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.:

AF XY:

0.0454

AC XY:

3380

AN XY:

74512

show subpopulations

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.:

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over