chr20-45947863-T-C

Variant names:

• chr20-45947863-T-C
• rs7679
• NM_022104.4:c.*108T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 106 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022104.4. 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
	PCIF1	NM_022104.4	MANE Select	c.*108T>C		3_prime_UTR	Exon 17 of 17	NP_071387.1	Q9H4Z3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PCIF1	ENST00000372409.8	TSL:1 MANE Select	c.*108T>C		3_prime_UTR	Exon 17 of 17	ENSP00000361486.3	Q9H4Z3
	PCIF1	ENST00000479348.2	TSL:1	c.*250T>C		3_prime_UTR	Exon 6 of 6	ENSP00000480607.1	A0A087WWZ2
	PCIF1	ENST00000904036.1		c.*108T>C		3_prime_UTR	Exon 17 of 17	ENSP00000574095.1

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

African (AFR) AF: 0.0360 AC: 1107 AN: 30768

American (AMR) AF: 0.0962 AC: 3107 AN: 32286

Ashkenazi Jewish (ASJ) AF: 0.177 AC: 4392 AN: 24818

East Asian (EAS) AF: 0.0151 AC: 545 AN: 36090

South Asian (SAS) AF: 0.197 AC: 15581 AN: 79206

European-Finnish (FIN) AF: 0.149 AC: 5090 AN: 34222

Middle Eastern (MID) AF: 0.132 AC: 732 AN: 5558

European-Non Finnish (NFE) AF: 0.186 AC: 201048 AN: 1080698

Other (OTH) AF: 0.165 AC: 9501 AN: 57702

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

African (AFR) AF: 0.0380 AC: 1578 AN: 41520

American (AMR) AF: 0.116 AC: 1780 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 610 AN: 3468

East Asian (EAS) AF: 0.0243 AC: 125 AN: 5150

South Asian (SAS) AF: 0.204 AC: 983 AN: 4810

European-Finnish (FIN) AF: 0.149 AC: 1574 AN: 10568

Middle Eastern (MID) AF: 0.134 AC: 39 AN: 292

European-Non Finnish (NFE) AF: 0.186 AC: 12649 AN: 67888

Other (OTH) AF: 0.139 AC: 292 AN: 2104

Alfa AF: 0.162 Hom.: 7353

Bravo AF: 0.122

Asia WGS AF: 0.120 AC: 416 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.5
DANN	Benign	0.64
PhyloP100		0.035
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7679; hg19: chr20-44576502; COSMIC: COSV107385063; COSMIC: COSV107385063;