rs7679

Positions:

• chr20-45947863-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022104.4(PCIF1):​c.*108T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,533,340 control chromosomes in the GnomAD database, including 23,743 homozygotes. 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 0.13 (1626 hom., cov: 32)
  • Exomes 𝑓: 0.17 (22117 hom.)
• Consequence: PCIF1 NM_022104.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0350

Genes affected

PCIF1 (HGNC:16200): (phosphorylated CTD interacting factor 1) Enables RNA polymerase II C-terminal domain phosphoserine binding activity; S-adenosyl-L-methionine binding activity; and mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity. Involved in mRNA methylation; negative regulation of translation; and positive regulation of translation. Located in intercellular bridge; microtubule cytoskeleton; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PCIF1	NM_022104.4	c.*108T>C		3_prime_UTR_variant	17/17	ENST00000372409.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PCIF1	ENST00000372409.8	c.*108T>C		3_prime_UTR_variant	17/17	1	NM_022104.4	P1
PCIF1	ENST00000479348.2	c.*250T>C		3_prime_UTR_variant	6/6	1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19801 AN: 151874 Hom.: 1626 Cov.: 32

Gnomad AFR AF: 0.0380

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.117

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.0246

Gnomad SAS AF: 0.204

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.138

GnomAD4 exome AF: 0.175 AC: 241103 AN: 1381348 Hom.: 22117 Cov.: 33 AF XY: 0.176 AC XY: 120081 AN XY: 683282

Gnomad4 AFR exome AF: 0.0360

Gnomad4 AMR exome AF: 0.0962

Gnomad4 ASJ exome AF: 0.177

Gnomad4 EAS exome AF: 0.0151

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.186

Gnomad4 OTH exome AF: 0.165

GnomAD4 genome AF: 0.130 AC: 19800 AN: 151992 Hom.: 1626 Cov.: 32 AF XY: 0.130 AC XY: 9690 AN XY: 74300

Gnomad4 AFR AF: 0.0380

Gnomad4 AMR AF: 0.116

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.0243

Gnomad4 SAS AF: 0.204

Gnomad4 FIN AF: 0.149

Gnomad4 NFE AF: 0.186

Gnomad4 OTH AF: 0.139

Alfa AF: 0.172 Hom.: 5146

Bravo AF: 0.122

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.64
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs7679; hg19: chr20-44576502;