Variant chr20-45941094-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_022104.4(PCIF1):c.560A>G(p.Lys187Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000169 in 1,614,210 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00018 ( 4 hom. )

Consequence

PCIF1
NM_022104.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.59

Variant links:

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]

PCIF1 links:

PCIF1 (HGNC:):

PCIF1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01133424).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PCIF1	NM_022104.4 linkuse as main transcript	c.560A>G	p.Lys187Arg	missense_variant	7/17	ENST00000372409.8	NP_071387.1	Q9H4Z3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PCIF1	ENST00000372409.8 linkuse as main transcript	c.560A>G	p.Lys187Arg	missense_variant	7/17	1	NM_022104.4	ENSP00000361486.3		Q9H4Z3

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000362

AC:

AN:

251406

Hom.:

AF XY:

0.000508

AC XY:

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00297

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000179

AC:

262

AN:

1461890

Hom.:

Cov.:

AF XY:

0.000250

AC XY:

182

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00290

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152320

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000688

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.000379

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 08, 2023

The c.560A>G (p.K187R) alteration is located in exon 7 (coding exon 5) of the PCIF1 gene. This alteration results from a A to G substitution at nucleotide position 560, causing the lysine (K) at amino acid position 187 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.019

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.059

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0029

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.98

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.23

REVEL

Benign

0.059

Sift

Benign

0.35

Sift4G

Benign

0.36

Polyphen

0.0020

Vest4

0.17

MutPred

0.28

Loss of methylation at K187 (P = 0.0043);

MVP

0.22

MPC

0.24

ClinPred

0.12

GERP RS

3.9

Varity_R

0.22

gMVP

0.43

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over