1-214651946-CTTTTT-CTTT

Variant names:

• chr1-214651946-CTT-C
• rs34322009
• NM_016343.4:c.8160+71_8160+72delTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_016343.4(CENPF):​c.8160+71_8160+72delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000913 in 1,017,556 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 27)
  • Exomes 𝑓: 0.00091 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CENPF NM_016343.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.169
• Publications: 0 publications found

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: Orphanet, Labcorp Genetics (formerly Invitae), Illumina, G2P, Genomics England PanelApp

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016343.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPF	NM_016343.4	MANE Select	c.8160+71_8160+72delTT		intron	N/A	NP_057427.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CENPF	ENST00000366955.8	TSL:1 MANE Select	c.8160+61_8160+62delTT		intron	N/A	ENSP00000355922.3	P49454
	CENPF	ENST00000934982.1		c.8280+61_8280+62delTT		intron	N/A	ENSP00000605041.1
	CENPF	ENST00000934983.1		c.8160+61_8160+62delTT		intron	N/A	ENSP00000605042.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 140694 Hom.: 0 Cov.: 27

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: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000913 AC: 929 AN: 1017556 Hom.: 0 AF XY: 0.000917 AC XY: 458 AN XY: 499290

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000476 AC: 11 AN: 23088

American (AMR) AF: 0.00252 AC: 42 AN: 16664

Ashkenazi Jewish (ASJ) AF: 0.000826 AC: 12 AN: 14524

East Asian (EAS) AF: 0.00108 AC: 32 AN: 29690

South Asian (SAS) AF: 0.00188 AC: 80 AN: 42576

European-Finnish (FIN) AF: 0.000849 AC: 34 AN: 40038

Middle Eastern (MID) AF: 0.000711 AC: 3 AN: 4220

European-Non Finnish (NFE) AF: 0.000837 AC: 673 AN: 804340

Other (OTH) AF: 0.000990 AC: 42 AN: 42416

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 140694 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 68032

African (AFR) AF: 0.00 AC: 0 AN: 39044

American (AMR) AF: 0.00 AC: 0 AN: 13954

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3314

East Asian (EAS) AF: 0.00 AC: 0 AN: 4888

South Asian (SAS) AF: 0.00 AC: 0 AN: 4418

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7708

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64274

Other (OTH) AF: 0.00 AC: 0 AN: 1918

Alfa AF: 0.00 Hom.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.17
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs34322009; hg19: chr1-214825289;