19-3530837-TCC-AGT

Variant names:

• chr19-3530837-TCC-AGT
• NM_016263.4:c.700_702delTCCinsAGT
• FZR1 p.235

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_016263.4(FZR1):​c.700_702delTCCinsAGT​(p.235) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S234S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FZR1 NM_016263.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.74
• Publications: 0 publications found

Genes affected

FZR1 (HGNC:24824): (fizzy and cell division cycle 20 related 1) Predicted to enable anaphase-promoting complex binding activity and ubiquitin ligase activator activity. Involved in anaphase-promoting complex-dependent catabolic process; mitotic G2 DNA damage checkpoint signaling; and positive regulation of protein metabolic process. Located in nuclear membrane and nucleoplasm. Colocalizes with anaphase-promoting complex. [provided by Alliance of Genome Resources, Apr 2022]

FZR1 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy 109

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016263.4. 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
	FZR1	NM_016263.4	MANE Select	c.700_702delTCCinsAGT	p.235	synonymous	N/A	NP_057347.2
	FZR1	NM_001136198.1		c.700_702delTCCinsAGT	p.235	synonymous	N/A	NP_001129670.1	Q9UM11-1
	FZR1	NM_001136197.1		c.433_435delTCCinsAGT	p.146	synonymous	N/A	NP_001129669.1	Q9UM11-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FZR1	ENST00000441788.7	TSL:1 MANE Select	c.700_702delTCCinsAGT	p.235	synonymous	N/A	ENSP00000410369.1	Q9UM11-2
	FZR1	ENST00000395095.7	TSL:1	c.700_702delTCCinsAGT	p.235	synonymous	N/A	ENSP00000378529.2	Q9UM11-1
	FZR1	ENST00000313639.8	TSL:1	c.433_435delTCCinsAGT	p.146	synonymous	N/A	ENSP00000321800.7	Q9UM11-3

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-3530835;