rs4979937

Positions:

• chr10-77979842-A-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.4024+299T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 152,036 control chromosomes in the GnomAD database, including 3,833 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3833 hom., cov: 32)
• Consequence: POLR3A NM_007055.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.02

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 10-77979842-A-T is Benign according to our data. Variant chr10-77979842-A-T is described in ClinVar as [Benign]. Clinvar id is 1265918.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR3A	NM_007055.4	c.4024+299T>A		intron_variant		ENST00000372371.8	NP_008986.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR3A	ENST00000372371.8	c.4024+299T>A		intron_variant		1	NM_007055.4	ENSP00000361446.3

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32236 AN: 151918 Hom.: 3832 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.378

Gnomad AMR AF: 0.245

Gnomad ASJ AF: 0.219

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.230

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.212 AC: 32254 AN: 152036 Hom.: 3833 Cov.: 32 AF XY: 0.215 AC XY: 16002 AN XY: 74302

Gnomad4 AFR AF: 0.181

Gnomad4 AMR AF: 0.246

Gnomad4 ASJ AF: 0.219

Gnomad4 EAS AF: 0.503

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.232

Alfa AF: 0.204 Hom.: 411

Bravo AF: 0.217

Asia WGS AF: 0.403 AC: 1399 AN: 3478

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

GeneDx

Mar 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.74

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: rs4979937; hg19: chr10-79739600;