12-106363847-ATTC-ATTCTTC

Variant names:

• chr12-106363847-A-ATTC
• NM_018082.6:c.73-17_73-15dupCTT

Variant summary

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

The NM_018082.6(POLR3B):​c.73-17_73-15dupCTT variant causes a intron 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: 32)
• Consequence: POLR3B NM_018082.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.367

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.73-17_73-15dupCTT		intron_variant	Intron 1 of 27	ENST00000228347.9	NP_060552.4
POLR3B	NM_001160708.2	c.-102-17_-102-15dupCTT		intron_variant	Intron 1 of 27		NP_001154180.1
POLR3B	XM_017019621.3	c.73-17_73-15dupCTT		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.73-23_73-22insTTC		intron_variant	Intron 1 of 27	1	NM_018082.6	ENSP00000228347.4
POLR3B	ENST00000539066.5	c.-102-23_-102-22insTTC		intron_variant	Intron 1 of 27	2		ENSP00000445721.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-106757625;