rs4979937

Variant names:

• chr10-77979842-A-T
• rs4979937
• NM_007055.4:c.4024+299T>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• odontoleukodystrophy

  Inheritance: AR Classification: DEFINITIVE, SUPPORTIVE Submitted by: Illumina, Orphanet
• Wiedemann-Rautenstrauch syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
• leukodystrophy, hypomyelinating, 7, with or without oligodontia and/or hypogonadotropic hypogonadism

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
• hypomyelination-cerebellar atrophy-hypoplasia of the corpus callosum syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• tremor-ataxia-central hypomyelination syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
POLR3A	NM_007055.4	c.4024+299T>A		intron_variant	Intron 30 of 30	ENST00000372371.8	NP_008986.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR3A	ENST00000372371.8	c.4024+299T>A		intron_variant	Intron 30 of 30	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

African (AFR) AF: 0.181 AC: 7519 AN: 41498

American (AMR) AF: 0.246 AC: 3751 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.219 AC: 759 AN: 3468

East Asian (EAS) AF: 0.503 AC: 2580 AN: 5128

South Asian (SAS) AF: 0.294 AC: 1412 AN: 4800

European-Finnish (FIN) AF: 0.178 AC: 1881 AN: 10576

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13448 AN: 67982

Other (OTH) AF: 0.232 AC: 490 AN: 2110

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

Mar 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.74
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4979937; hg19: chr10-79739600;