Variant 1-214657139-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate

The NM_016343.4(CENPF):c.8692C>T(p.Arg2898Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

CENPF
NM_016343.4 stop_gained

Scores

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 0.766

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:

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ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 1-214657139-C-T is Pathogenic according to our data. Variant chr1-214657139-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 190387.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-214657139-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
CENPF	NM_016343.4 linkuse as main transcript	c.8692C>T	p.Arg2898Ter	stop_gained	18/20	ENST00000366955.8	NP_057427.3
CENPF	XM_017000086.3 linkuse as main transcript	c.8692C>T	p.Arg2898Ter	stop_gained	18/20		XP_016855575.1
CENPF	XM_011509082.4 linkuse as main transcript	c.8515C>T	p.Arg2839Ter	stop_gained	17/19		XP_011507384.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
CENPF	ENST00000366955.8 linkuse as main transcript	c.8692C>T	p.Arg2898Ter	stop_gained	18/20	1	NM_016343.4	ENSP00000355922	P2
CENPF	ENST00000706765.1 linkuse as main transcript	c.8515C>T	p.Arg2839Ter	stop_gained	17/19			ENSP00000516538	A2
CENPF	ENST00000469862.1 linkuse as main transcript	n.463C>T		non_coding_transcript_exon_variant	2/2	2
CENPF	ENST00000706766.1 linkuse as main transcript	n.791C>T		non_coding_transcript_exon_variant	3/5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000410

AC:

AN:

1461858

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000611

Hom.:

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Stromme syndrome

Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Mar 01, 2015	- -
Pathogenic, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	May 20, 2022	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.63

BayesDel_noAF

Pathogenic

0.28

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Benign

0.047

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.24

MutationTaster

Benign

1.0

Vest4

0.19

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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