chr10-77979773-C-T

Position:

• chr10-77979773-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007055.4(POLR3A):​c.4024+368G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.32 in 152,102 control chromosomes in the GnomAD database, including 9,778 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 0.32 (9778 hom., cov: 32)
• Consequence: POLR3A NM_007055.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR3A	NM_007055.4	c.4024+368G>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+368G>A		intron_variant		1	NM_007055.4	ENSP00000361446.3

Frequencies

GnomAD3 genomes AF: 0.320 AC: 48606 AN: 151984 Hom.: 9743 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.377

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.518

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.178

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.307

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

GnomAD4 genome AF: 0.320 AC: 48699 AN: 152102 Hom.: 9778 Cov.: 32 AF XY: 0.319 AC XY: 23733 AN XY: 74362

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.518

Gnomad4 SAS AF: 0.297

Gnomad4 FIN AF: 0.178

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.309

Alfa AF: 0.243 Hom.: 1130

Bravo AF: 0.339

Asia WGS AF: 0.444 AC: 1541 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.9
DANN	Benign	0.28

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: rs4979936; hg19: chr10-79739531;