NM_021128.5:c.*53G>C

Variant names:

• chr11-840319-C-G
• rs3059
• NM_021128.5:c.*53G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021128.5(POLR2L):​c.*53G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POLR2L NM_021128.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.587
• Publications: 48 publications found

Genes affected

POLR2L (HGNC:9199): (RNA polymerase II, I and III subunit L) This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains four conserved cysteines characteristic of an atypical zinc-binding domain. Like its counterpart in yeast, this subunit may be shared by the other two DNA-directed RNA polymerases. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021128.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR2L	NM_021128.5	MANE Select	c.*53G>C		3_prime_UTR	Exon 2 of 2	NP_066951.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR2L	ENST00000322028.5	TSL:1 MANE Select	c.*53G>C		3_prime_UTR	Exon 2 of 2	ENSP00000324124.4
	POLR2L	ENST00000534030.1	TSL:4	n.*53G>C		non_coding_transcript_exon	Exon 2 of 3	ENSP00000432807.1
	POLR2L	ENST00000534030.1	TSL:4	n.*53G>C		3_prime_UTR	Exon 2 of 3	ENSP00000432807.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1037968 Hom.: 0 Cov.: 13 AF XY: 0.00 AC XY: 0 AN XY: 524430

African (AFR) AF: 0.00 AC: 0 AN: 24958

American (AMR) AF: 0.00 AC: 0 AN: 37730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20316

East Asian (EAS) AF: 0.00 AC: 0 AN: 35964

South Asian (SAS) AF: 0.00 AC: 0 AN: 70420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49158

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4808

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 748672

Other (OTH) AF: 0.00 AC: 0 AN: 45942

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 56429

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.7
DANN	Benign	0.52
PhyloP100		-0.59
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Other links and lift over

dbSNP: rs3059; hg19: chr11-840319;