rs144237457

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

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. 15/21 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

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

Stromme syndrome
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Illumina, Genomics England PanelApp, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

CENPF links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

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

BP6

Variant 1-214641955-A-G is Benign according to our data. Variant chr1-214641955-A-G is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 434704.

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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
CENPF	NM_016343.4 link	c.3617A>G	p.Tyr1206Cys	missense_variant	Exon 12 of 20	ENST00000366955.8	NP_057427.3
CENPF	XM_017000086.3 link	c.3617A>G	p.Tyr1206Cys	missense_variant	Exon 12 of 20		XP_016855575.1
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
CENPF	ENST00000706765.1 link	c.3617A>G	p.Tyr1206Cys	missense_variant	Exon 12 of 19			ENSP00000516538.1

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

GnomAD2 exomes

AF:

0.00255

AC:

589

AN:

231036

AF XY:

0.00256

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 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

African (AFR)

AF:

0.000436

AC:

AN:

32092

American (AMR)

AF:

0.00136

AC:

AN:

39804

Ashkenazi Jewish (ASJ)

AF:

0.00777

AC:

195

AN:

25094

East Asian (EAS)

AF:

0.00

AC:

AN:

39630

South Asian (SAS)

AF:

0.000757

AC:

AN:

81898

European-Finnish (FIN)

AF:

0.00236

AC:

125

AN:

52898

Middle Eastern (MID)

AF:

0.00195

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00370

AC:

4094

AN:

1106990

Other (OTH)

AF:

0.00333

AC:

198

AN:

59480

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

248

496

743

991

1239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

162

324

486

648

810

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00218

AC:

332

AN:

152326

Hom.:

Cov.:

AF XY:

0.00184

AC XY:

137

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000625

AC:

AN:

41576

American (AMR)

AF:

0.00333

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000622

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00160

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00306

AC:

208

AN:

68026

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00311

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

May 01, 2018

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 13, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

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

(source)

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

PhyloP100

0.17

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

Mutation Taster

=85/15

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over