chr10-77978480-A-G

Position:

• chr10-77978480-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
POLR3A	NM_007055.4	c.4025-854T>C		intron_variant		ENST00000372371.8	NP_008986.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR3A	ENST00000372371.8	c.4025-854T>C		intron_variant		1	NM_007055.4	ENSP00000361446	P1

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

Gnomad4 AFR AF: 0.302

Gnomad4 AMR AF: 0.254

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.516

Gnomad4 SAS AF: 0.295

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.248

Alfa AF: 0.221 Hom.: 497

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

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: rs7905170; hg19: chr10-79738238;