rs398122850

Positions:

• chrX-137566853-T-TGCCGCC

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_003413.4(ZIC3):​c.165_166insGCCGCC​(p.Ala54_Ala55dup) variant causes a conservative inframe insertion change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 25)
• Consequence: ZIC3 NM_003413.4 conservative_inframe_insertion
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.98

Genes affected

ZIC3 (HGNC:12874): (Zic family member 3) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. This nuclear protein probably functions as a transcription factor in early stages of left-right body axis formation. Mutations in this gene cause X-linked visceral heterotaxy, which includes congenital heart disease and left-right axis defects in organs. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_003413.4.
• PP5: Variant X-137566853-T-TGCCGCC is Pathogenic according to our data. Variant chrX-137566853-T-TGCCGCC is described in ClinVar as [Pathogenic]. Clinvar id is 29955.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZIC3	NM_003413.4	c.165_166insGCCGCC	p.Ala54_Ala55dup	conservative_inframe_insertion	1/3	ENST00000287538.10	NP_003404.1
ZIC3	NM_001330661.1	c.165_166insGCCGCC	p.Ala54_Ala55dup	conservative_inframe_insertion	1/3		NP_001317590.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZIC3	ENST00000287538.10	c.165_166insGCCGCC	p.Ala54_Ala55dup	conservative_inframe_insertion	1/3	1	NM_003413.4	ENSP00000287538.5
ZIC3	ENST00000370606.3	c.165_166insGCCGCC	p.Ala54_Ala55dup	conservative_inframe_insertion	1/3	5		ENSP00000359638.3

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 25

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

VACTERL association, X-linked, with or without hydrocephalus Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

May 01, 2010

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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: rs398122850; hg19: chrX-136649012;