rs757575602

chr1-214614833-TTGAAAATGAAAAAACCGAGGGTACAAACC-T

Variant summary

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

The NM_016343.4(CENPF):c.171_199del(p.Asn57LysfsTer11) variant causes a frameshift, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000263 in 152,094 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CENPF
NM_016343.4 frameshift, splice_region

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 9.25

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 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 1-214614833-TTGAAAATGAAAAAACCGAGGGTACAAACC-T is Pathogenic according to our data. Variant chr1-214614833-TTGAAAATGAAAAAACCGAGGGTACAAACC-T is described in ClinVar as [Pathogenic]. Clinvar id is 224501.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-214614833-TTGAAAATGAAAAAACCGAGGGTACAAACC-T is described in Lovd as [Likely_pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
CENPF	NM_016343.4 linkuse as main transcript	c.171_199del	p.Asn57LysfsTer11	frameshift_variant, splice_region_variant	3/20	ENST00000366955.8
CENPF	XM_011509082.4 linkuse as main transcript	c.171_199del	p.Asn57LysfsTer11	frameshift_variant, splice_region_variant	3/19
CENPF	XM_017000086.3 linkuse as main transcript	c.171_199del	p.Asn57LysfsTer11	frameshift_variant, splice_region_variant	3/20

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
CENPF	ENST00000366955.8 linkuse as main transcript	c.171_199del	p.Asn57LysfsTer11	frameshift_variant, splice_region_variant	3/20	1	NM_016343.4	P2
CENPF	ENST00000706765.1 linkuse as main transcript	c.171_199del	p.Asn57LysfsTer11	frameshift_variant, splice_region_variant	3/19			A2
CENPF	ENST00000464322.5 linkuse as main transcript	n.339_367del		splice_region_variant, non_coding_transcript_exon_variant	3/3	2
CENPF	ENST00000706764.1 linkuse as main transcript	n.349_377del		splice_region_variant, non_coding_transcript_exon_variant	3/7

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000364

AC:

AN:

219866

Hom.:

AF XY:

0.0000502

AC XY:

AN XY:

119504

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000762

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000325

AC:

AN:

1415568

Hom.:

AF XY:

0.0000256

AC XY:

AN XY:

702122

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:

0.00

Gnomad4 FIN exome

AF:

0.0000190

Gnomad4 NFE exome

AF:

0.0000412

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

Bravo

AF:

0.0000340

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	Aug 25, 2017	- -
Pathogenic, criteria provided, single submitter	clinical testing	Baylor Genetics	Aug 29, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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