19-3530839-C-G

Variant names:

• chr19-3530839-C-G
• NM_016263.4:c.702C>G
• FZR1 p.Ser234Ser

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_016263.4(FZR1):​c.702C>G​(p.Ser234Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: -4.58
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP7: Synonymous conserved (PhyloP=-4.58 with no splicing effect.

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.702C>G	p.Ser234Ser	synonymous	Exon 8 of 14	NP_057347.2
	FZR1	NM_001136198.1		c.702C>G	p.Ser234Ser	synonymous	Exon 7 of 13	NP_001129670.1	Q9UM11-1
	FZR1	NM_001136197.1		c.435C>G	p.Ser145Ser	synonymous	Exon 5 of 11	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.702C>G	p.Ser234Ser	synonymous	Exon 8 of 14	ENSP00000410369.1	Q9UM11-2
	FZR1	ENST00000395095.7	TSL:1	c.702C>G	p.Ser234Ser	synonymous	Exon 7 of 13	ENSP00000378529.2	Q9UM11-1
	FZR1	ENST00000313639.8	TSL:1	c.435C>G	p.Ser145Ser	synonymous	Exon 5 of 11	ENSP00000321800.7	Q9UM11-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.86
DANN	Benign	0.77
PhyloP100		-4.6

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

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: chr19-3530837;