5-90501917-C-T

Variant names:

• chr5-90501917-C-T
• NM_006467.3:c.367C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006467.3(POLR3G):​c.367C>T​(p.Pro123Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: POLR3G NM_006467.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.204
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.018274754).
• BP6: Variant 5-90501917-C-T is Benign according to our data. Variant chr5-90501917-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2474328.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006467.3. 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
	POLR3G	NM_006467.3	MANE Select	c.367C>T	p.Pro123Ser	missense	Exon 6 of 8	NP_006458.2	O15318
	POLR3G	NM_001370351.1		c.367C>T	p.Pro123Ser	missense	Exon 6 of 8	NP_001357280.1	O15318
	POLR3G	NM_001370354.1		c.367C>T	p.Pro123Ser	missense	Exon 6 of 8	NP_001357283.1	O15318

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR3G	ENST00000651687.1	MANE Select	c.367C>T	p.Pro123Ser	missense	Exon 6 of 8	ENSP00000498469.1	O15318
	POLR3G	ENST00000504930.5	TSL:2	c.367C>T	p.Pro123Ser	missense	Exon 6 of 8	ENSP00000421637.1	O15318
	POLR3G	ENST00000859024.1		c.367C>T	p.Pro123Ser	missense	Exon 6 of 8	ENSP00000529083.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461060 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726842

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39626

South Asian (SAS) AF: 0.00 AC: 0 AN: 86170

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111506

Other (OTH) AF: 0.00 AC: 0 AN: 60350

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	6.1
DANN	Benign	0.40
DEOGEN2	Benign	0.021	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0062	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.018	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		-0.20
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.024
Sift	Benign	0.62	T
Sift4G	Benign	0.70	T
Polyphen		0.0060	B
Vest4		0.083
MutPred		0.21		Gain of phosphorylation at P123 (P = 0.0073)
MVP		0.14
MPC		0.076
ClinPred		0.025	T
GERP RS		1.6
Varity_R		0.026
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

hg19: chr5-89797734;