rs144237457

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_016343.4(CENPF):c.3617A>G(p.Tyr1206Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00319 in 1,595,864 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 10 hom. )

Consequence

CENPF
NM_016343.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:1

Conservation

PhyloP100: 0.175

Variant links:

Genes affected

CENPF (HGNC:1857): (centromere protein F) This gene encodes a protein that associates with the centromere-kinetochore complex. The protein is a component of the nuclear matrix during the G2 phase of interphase. In late G2 the protein associates with the kinetochore and maintains this association through early anaphase. It localizes to the spindle midzone and the intracellular bridge in late anaphase and telophase, respectively, and is thought to be subsequently degraded. The localization of this protein suggests that it may play a role in chromosome segregation during mitotis. It is thought to form either a homodimer or heterodimer. Autoantibodies against this protein have been found in patients with cancer or graft versus host disease. [provided by RefSeq, Jul 2008]

CENPF links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003427714).

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00218 (332/152326) while in subpopulation AMR AF= 0.00333 (51/15300). AF 95% confidence interval is 0.00272. There are 0 homozygotes in gnomad4. There are 137 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CENPF	NM_016343.4 link	c.3617A>G	p.Tyr1206Cys	missense_variant	Exon 12 of 20	ENST00000366955.8	NP_057427.3	P49454
CENPF	XM_017000086.3 link	c.3617A>G	p.Tyr1206Cys	missense_variant	Exon 12 of 20		XP_016855575.1	P49454
CENPF	XM_011509082.4 link	c.3617A>G	p.Tyr1206Cys	missense_variant	Exon 12 of 19		XP_011507384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CENPF	ENST00000366955.8 link	c.3617A>G	p.Tyr1206Cys	missense_variant	Exon 12 of 20	1	NM_016343.4	ENSP00000355922.3		P49454
CENPF	ENST00000706765.1 link	c.3617A>G	p.Tyr1206Cys	missense_variant	Exon 12 of 19			ENSP00000516538.1		A0A9L9PXU7

Frequencies

GnomAD3 genomes

AF:

0.00218

AC:

332

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000627

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00334

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00306

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00255

AC:

589

AN:

231036

Hom.:

AF XY:

0.00256

AC XY:

321

AN XY:

125332

show subpopulations

Gnomad AFR exome

AF:

0.000530

Gnomad AMR exome

AF:

0.000995

Gnomad ASJ exome

AF:

0.00831

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000539

Gnomad FIN exome

AF:

0.00210

Gnomad NFE exome

AF:

0.00372

Gnomad OTH exome

AF:

0.00399

GnomAD4 exome

AF:

0.00329

AC:

4753

AN:

1443538

Hom.:

Cov.:

AF XY:

0.00321

AC XY:

2304

AN XY:

717586

show subpopulations

Gnomad4 AFR exome

AF:

0.000436

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00777

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000757

Gnomad4 FIN exome

AF:

0.00236

Gnomad4 NFE exome

AF:

0.00370

Gnomad4 OTH exome

AF:

0.00333

GnomAD4 genome

AF:

0.00218

AC:

332

AN:

152326

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

137

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.000625

Gnomad4 AMR

AF:

0.00333

Gnomad4 ASJ

AF:

0.00634

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.00306

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00332

Hom.:

Bravo

AF:

0.00235

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00263

AC:

319

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Nov 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 01, 2018

CeGaT Center for Human Genetics Tuebingen

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Uncertain:1

Nov 29, 2016

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Stromme syndrome

Uncertain:1

Sep 27, 2019

Baylor Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.67

CADD

Benign

5.3

DANN

Benign

0.80

DEOGEN2

Benign

0.023

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.69

M_CAP

Benign

0.0062

MetaRNN

Benign

0.0034

MetaSVM

Benign

-0.95

PrimateAI

Benign

0.34

PROVEAN

Benign

-1.6

REVEL

Benign

0.015

Sift

Benign

0.15

Sift4G

Benign

0.19

Polyphen

0.13

Vest4

0.26

MVP

0.36

MPC

0.067

ClinPred

0.0019

GERP RS

1.7

Varity_R

0.075

gMVP

0.22

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

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