11-46703166-CAGTGGTGACAGA-CAGTGGTGACAGAAGTGGTGACAGA

Position:

• chr11-46703166-CAGTGGTGACAGA-CAGTGGTGACAGAAGTGGTGACAGA

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_024741.3(ZNF408):​c.581_592dupTGACAGAAGTGG​(p.Val194_Val197dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ZNF408 NM_024741.3 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381

Genes affected

ZNF408 (HGNC:20041): (zinc finger protein 408) The protein encoded by this gene contains ten tandem zinc fingers and an N-terminal SET domain, so it is likely a DNA binding protein that interacts with other proteins. In adults, the encoded protein is expressed most highly in retina. Consequently, defects in this gene have been associated with familial exudative vitreoretinopathy (FEVR) and retinitis pigmentosa (RP). [provided by RefSeq, Dec 2016]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_024741.3.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF408	NM_024741.3	c.581_592dupTGACAGAAGTGG	p.Val194_Val197dup	disruptive_inframe_insertion	4/5	ENST00000311764.3	NP_079017.1
ZNF408	NM_001184751.2	c.557_568dupTGACAGAAGTGG	p.Val186_Val189dup	disruptive_inframe_insertion	4/5		NP_001171680.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF408	ENST00000311764.3	c.581_592dupTGACAGAAGTGG	p.Val194_Val197dup	disruptive_inframe_insertion	4/5	1	NM_024741.3	ENSP00000309606.2
ZNF408	ENST00000527008.1	n.458_469dupTGACAGAAGTGG		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs148055528; hg19: chr11-46724716;