rs747528688

Variant names:

• chr22-37959350-G-A
• rs747528688
• NM_021974.5:c.95G>A

Your query was ambiguous. Multiple possible variants found:

• chr22-37959350-G-A
• chr22-37959350-G-C
• chr22-37959350-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021974.5(POLR2F):​c.95G>A​(p.Gly32Asp) 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. 9/14 in silico tools predict 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: 32)
• Consequence: POLR2F NM_021974.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.97

Genes affected

POLR2F (HGNC:9193): (RNA polymerase II, I and III subunit F) This gene encodes the sixth largest subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. In yeast, this polymerase subunit, in combination with at least two other subunits, forms a structure that stabilizes the transcribing polymerase on the DNA template. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15162945).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLR2F	NM_021974.5	c.95G>A	p.Gly32Asp	missense_variant	Exon 3 of 5	ENST00000442738.7	NP_068809.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLR2F	ENST00000442738.7	c.95G>A	p.Gly32Asp	missense_variant	Exon 3 of 5	1	NM_021974.5	ENSP00000403852.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	24
DANN	Benign	0.61
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.24
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.0031	T
MetaRNN	Benign	0.15	T
Sift4G	Benign	0.21	T
Vest4		0.16
MVP		0.73
ClinPred		0.74	D
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs747528688; hg19: chr22-38355357;