12-106358132-GAGTGA-GAGTGAAGTGA

Variant names:

• chr12-106358132-G-GAGTGA
• rs139244819
• NM_018082.6:c.72+184_72+188dupTGAAG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001160708.2(POLR3B):​c.-190_-186dupTGAAG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 26)
• Consequence: POLR3B NM_001160708.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.962

Genes affected

POLR3B (HGNC:30348): (RNA polymerase III subunit B) This gene encodes the second largest subunit of RNA polymerase III, the polymerase responsible for synthesizing transfer and small ribosomal RNAs in eukaryotes. The largest subunit and the encoded protein form the catalytic center of RNA polymerase III. Mutations in this gene are a cause of hypomyelinating leukodystrophy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR3B	NM_018082.6	c.72+184_72+188dupTGAAG		intron_variant	Intron 1 of 27	ENST00000228347.9	NP_060552.4
POLR3B	NM_001160708.2	c.-190_-186dupTGAAG		5_prime_UTR_variant	Exon 1 of 28		NP_001154180.1
POLR3B	XM_017019621.3	c.72+184_72+188dupTGAAG		intron_variant	Intron 1 of 25		XP_016875110.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR3B	ENST00000228347.9	c.72+184_72+188dupTGAAG		intron_variant	Intron 1 of 27	1	NM_018082.6	ENSP00000228347.4
POLR3B	ENST00000539066	c.-190_-186dupTGAAG		5_prime_UTR_variant	Exon 1 of 28	2		ENSP00000445721.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139244819; hg19: chr12-106751910;