5-90501939-G-A

Position:

• chr5-90501939-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_006467.3(POLR3G):​c.389G>A​(p.Gly130Asp) variant causes a missense 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. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: POLR3G NM_006467.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.310

Genes affected

POLR3G (HGNC:30075): (RNA polymerase III subunit G) Enables chromatin binding activity. Involved in positive regulation of innate immune response; positive regulation of interferon-beta production; and transcription by RNA polymerase III. Acts upstream of or within cell population proliferation. Located in cytosol and nuclear body. Part of RNA polymerase III complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.047492594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLR3G	NM_006467.3	c.389G>A	p.Gly130Asp	missense_variant	6/8	ENST00000651687.1	NP_006458.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLR3G	ENST00000651687.1	c.389G>A	p.Gly130Asp	missense_variant	6/8		NM_006467.3	ENSP00000498469.1
POLR3G	ENST00000504930.5	c.389G>A	p.Gly130Asp	missense_variant	6/8	2		ENSP00000421637.1
POLR3G	ENST00000503373.5	c.389G>A	p.Gly130Asp	missense_variant	6/8	4		ENSP00000422892.1
POLR3G	ENST00000399107.6	n.418G>A		non_coding_transcript_exon_variant	6/8	2		ENSP00000382058.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 01, 2021

The c.389G>A (p.G130D) alteration is located in exon 6 (coding exon 5) of the POLR3G gene. This alteration results from a G to A substitution at nucleotide position 389, causing the glycine (G) at amino acid position 130 to be replaced by an aspartic acid (D). 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	Benign	0.089
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	14
DANN	Benign	0.50
DEOGEN2	Benign	0.0080	T;T;T
Eigen	Benign	-0.98
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.58	T;T;.
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.047	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.065	.;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.36	N;N;N
REVEL	Benign	0.12
Sift	Benign	0.64	T;T;T
Sift4G	Benign	0.53	T;T;T
Polyphen		0.035	.;B;B
Vest4		0.067
MutPred		0.22		Loss of MoRF binding (P = 0.0424);Loss of MoRF binding (P = 0.0424);Loss of MoRF binding (P = 0.0424);
MVP		0.12
MPC		0.11
ClinPred		0.022	T
GERP RS		-2.1
Varity_R		0.032

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.19		Details are displayed if max score is > 0.2

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: chr5-89797756;