Variant chr10-77975715-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.05

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 -20 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_multiple_submitters_no_conflicts, 2 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 linkuse as main transcript	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 linkuse as main transcript	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.:

show subpopulations

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:

AN:

Hom.:

Cov.:

AF XY:

0.125

AC XY:

AN XY:

show subpopulations

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.:

AF XY:

0.158

AC XY:

11770

AN XY:

74392

show subpopulations

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:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

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