NM_018082.6:c.72+184_72+188dupTGAAG

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_018082.6(POLR3B):​c.72+184_72+188dupTGAAG 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: 26)
• Consequence: POLR3B NM_018082.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.962
• Publications: 1 publications found

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]

POLR3B Gene-Disease associations (from GenCC):

• POLR3B-related disorder

  Inheritance: AD, AR Classification: DEFINITIVE Submitted by: ClinGen
• hypomyelinating leukodystrophy 8 with or without oligodontia and-or hypogonadotropic hypogonadism

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, G2P
• neurodevelopmental disorder

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: G2P
• Charcot-Marie-Tooth disease, demyelinating, IIA 1I

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• endosteal sclerosis-cerebellar hypoplasia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hypomyelination-hypogonadotropic hypogonadism-hypodontia syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000297327 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018082.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3B	NM_018082.6	MANE Select	c.72+184_72+188dupTGAAG		intron	N/A	NP_060552.4
	POLR3B	NM_001160708.2		c.-190_-186dupTGAAG		5_prime_UTR	Exon 1 of 28	NP_001154180.1	Q9NW08-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3B	ENST00000228347.9	TSL:1 MANE Select	c.72+184_72+188dupTGAAG		intron	N/A	ENSP00000228347.4	Q9NW08-1
	POLR3B	ENST00000539066.5	TSL:2	c.-190_-186dupTGAAG		5_prime_UTR	Exon 1 of 28	ENSP00000445721.1	Q9NW08-2
	POLR3B	ENST00000970165.1		c.72+184_72+188dupTGAAG		intron	N/A	ENSP00000640224.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Cov.: 23

GnomAD4 genome Cov.: 26

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.96

Splicing

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

Other links and lift over

dbSNP: rs139244819; hg19: chr12-106751910;