rs1559257942

Variant names:

• chr1-145977998-G-A
• rs1559257942
• NM_032305.3:c.472G>A

Your query was ambiguous. Multiple possible variants found:

• chr1-145977998-G-A
• chr1-145977998-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032305.3(POLR3GL):​c.472G>A​(p.Glu158Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POLR3GL NM_032305.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.61

Genes affected

POLR3GL (HGNC:28466): (RNA polymerase III subunit GL) Predicted to enable chromatin binding activity. Involved in transcription by RNA polymerase III. Located in nucleus. Part of RNA polymerase III complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000280778 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19681442).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR3GL	NM_032305.3	c.472G>A	p.Glu158Lys	missense_variant	Exon 7 of 8	ENST00000369314.2	NP_115681.1
POLR3GL	NM_001330685.2	c.403G>A	p.Glu135Lys	missense_variant	Exon 6 of 7		NP_001317614.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR3GL	ENST00000369314.2	c.472G>A	p.Glu158Lys	missense_variant	Exon 7 of 8	1	NM_032305.3	ENSP00000358320.1
ENSG00000280778	ENST00000625258.1	c.*187G>A		downstream_gene_variant		5		ENSP00000487094.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 11, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.472G>A (p.E158K) alteration is located in exon 7 (coding exon 6) of the POLR3GL gene. This alteration results from a G to A substitution at nucleotide position 472, causing the glutamic acid (E) at amino acid position 158 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.77
BayesDel_noAF	Pathogenic	0.51
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.037	T;T
LIST_S2	Uncertain	0.92	D;D
MetaRNN	Benign	0.20	T;T
PhyloP100		5.6
PROVEAN	Benign	-2.3	N;N
Sift	Benign	0.14	T;T
Sift4G	Benign	0.081	T;T
Vest4		0.38
gMVP		0.65

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

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Other links and lift over

dbSNP: rs1559257942; hg19: chr1-145457089;