rs7905170

Variant names:

• chr10-77978480-A-G
• rs7905170
• NM_007055.4:c.4025-854T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007055.4(POLR3A):​c.4025-854T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,934 control chromosomes in the GnomAD database, including 5,129 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.25 (5129 hom., cov: 31)
• Consequence: POLR3A NM_007055.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.586
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR3A	NM_007055.4	c.4025-854T>C		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.4025-854T>C		intron_variant	Intron 30 of 30	1	NM_007055.4	ENSP00000361446.3

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37435 AN: 151816 Hom.: 5111 Cov.: 31

Gnomad AFR AF: 0.302

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.516

Gnomad SAS AF: 0.296

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.245

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

GnomAD4 genome AF: 0.247 AC: 37499 AN: 151934 Hom.: 5129 Cov.: 31 AF XY: 0.248 AC XY: 18427 AN XY: 74236

African (AFR) AF: 0.302 AC: 12511 AN: 41410

American (AMR) AF: 0.254 AC: 3872 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 771 AN: 3466

East Asian (EAS) AF: 0.516 AC: 2658 AN: 5150

South Asian (SAS) AF: 0.295 AC: 1420 AN: 4810

European-Finnish (FIN) AF: 0.178 AC: 1886 AN: 10570

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.198 AC: 13436 AN: 67958

Other (OTH) AF: 0.248 AC: 521 AN: 2104

Alfa AF: 0.223 Hom.: 528

Bravo AF: 0.255

Asia WGS AF: 0.429 AC: 1488 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.41
DANN	Benign	0.40
PhyloP100		-0.59
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: rs7905170; hg19: chr10-79738238;