chr5-90474112-C-T

Variant names:

• chr5-90474112-C-T
• rs1488746577
• NM_203406.2:c.181G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001370354.1(POLR3G):​c.-250C>T variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.00000253 in 1,579,278 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: POLR3G NM_001370354.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.35
• Publications: 1 publications found

Genes affected

MBLAC2 (HGNC:33711): (metallo-beta-lactamase domain containing 2) Enables palmitoyl-CoA hydrolase activity. Located in endoplasmic reticulum membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3016339).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001370354.1. 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
	MBLAC2	NM_203406.2	MANE Select	c.181G>A	p.Gly61Ser	missense	Exon 1 of 2	NP_981951.2	Q68D91-1
	POLR3G	NM_001370354.1		c.-250C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001357283.1	O15318
	POLR3G	NM_001370354.1		c.-250C>T		5_prime_UTR	Exon 1 of 8	NP_001357283.1	O15318

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBLAC2	ENST00000316610.7	TSL:1 MANE Select	c.181G>A	p.Gly61Ser	missense	Exon 1 of 2	ENSP00000314776.6	Q68D91-1
	POLR3G	ENST00000859024.1		c.-240C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	ENSP00000529083.1
	POLR3G	ENST00000959308.1		c.-360C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000629367.1

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152144 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 7.01e-7 AC: 1 AN: 1427134 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 706638

African (AFR) AF: 0.0000303 AC: 1 AN: 33014

American (AMR) AF: 0.00 AC: 0 AN: 38272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25374

East Asian (EAS) AF: 0.00 AC: 0 AN: 38252

South Asian (SAS) AF: 0.00 AC: 0 AN: 82198

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1094592

Other (OTH) AF: 0.00 AC: 0 AN: 59182

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152144 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74314

African (AFR) AF: 0.0000724 AC: 3 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.040
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.76	T
M_CAP	Uncertain	0.091	D
MetaRNN	Benign	0.30	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		4.4
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.39	N
REVEL	Benign	0.12
Sift	Benign	0.12	T
Sift4G	Benign	0.37	T
Polyphen		0.11	B
Vest4		0.54
MutPred		0.41		Loss of helix (P = 0.028)
MVP		0.43
MPC		0.41
ClinPred		0.90	D
GERP RS		5.4
PromoterAI		-0.11	Neutral
Varity_R		0.36
gMVP		0.88
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1488746577; hg19: chr5-89769929;