rs748325646

chrX-137566825-ACGCCGCCGCCGCCGC-AchrX-137566825-ACGCCGCCGCCGCCGC-ACGCchrX-137566825-ACGCCGCCGCCGCCGC-ACGCCGCchrX-137566825-ACGCCGCCGCCGCCGC-ACGCCGCCGCchrX-137566825-ACGCCGCCGCCGCCGC-ACGCCGCCGCCGCchrX-137566825-ACGCCGCCGCCGCCGC-ACGCCGCCGCCGCCGCCGCchrX-137566825-ACGCCGCCGCCGCCGC-ACGCCGCCGCCGCCGCCGCCGCchrX-137566825-ACGCCGCCGCCGCCGC-ACGCCGCCGCCGCCGCCGCCGCCGCchrX-137566825-ACGCCGCCGCCGCCGC-ACGCCGCCGCCGCCGCCGCCGCCGCCGC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP3 BS2

The NM_003413.4(ZIC3):c.147_161del(p.Ala51_Ala55del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 1,160,637 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000027 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.000012 (0 hom. 2 hem.)
• Consequence: ZIC3 NM_003413.4 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41

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 Likely_benign. Variant got -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_003413.4
• BS2: High Hemizygotes in GnomAd at 2 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZIC3	NM_003413.4	c.147_161del	p.Ala51_Ala55del	inframe_deletion	1/3	ENST00000287538.10
ZIC3	NM_001330661.1	c.147_161del	p.Ala51_Ala55del	inframe_deletion	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZIC3	ENST00000287538.10	c.147_161del	p.Ala51_Ala55del	inframe_deletion	1/3	1	NM_003413.4	P1
ZIC3	ENST00000370606.3	c.147_161del	p.Ala51_Ala55del	inframe_deletion	1/3	5

Frequencies

GnomAD3 genomes AF: 0.0000268 AC: 3 AN: 111760 Hom.: 0 Cov.: 24 AF XY: 0.0000586 AC XY: 2 AN XY: 34146

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: 0.0000567

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000124 AC: 13 AN: 1048877 Hom.: 0 AF XY: 0.00000586 AC XY: 2 AN XY: 341519

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000134

Gnomad4 OTH exome AF: 0.0000451

GnomAD4 genome AF: 0.0000268 AC: 3 AN: 111760 Hom.: 0 Cov.: 24 AF XY: 0.0000586 AC XY: 2 AN XY: 34146

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000567

Gnomad4 OTH AF: 0.00

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: rs748325646; hg19: chrX-136648984;