X-137566825-ACGCCGCCGCCGCCGC-ACGC

Variant names:

• chrX-137566825-ACGCCGCCGCCGC-A
• rs748325646
• NM_003413.4:c.150_161delCGCCGCCGCCGC

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_003413.4(ZIC3):​c.150_161delCGCCGCCGCCGC​(p.Ala51_Ala54del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000681 in 1,160,626 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 24 hemizygotes in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, 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.

• Frequency:
  • Genomes: 𝑓 0.000081 (0 hom., 2 hem., cov: 24)
  • Exomes 𝑓: 0.000067 (0 hom. 22 hem.)
• Consequence: ZIC3 NM_003413.4 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 0 publications found

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]

LINC02931 (HGNC:55853): (long intergenic non-protein coding RNA 2931)

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_003413.4
• BS2: High Hemizygotes in GnomAd4 at 2 XL gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003413.4. 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
	ZIC3	NM_003413.4	MANE Select	c.150_161delCGCCGCCGCCGC	p.Ala51_Ala54del	disruptive_inframe_deletion	Exon 1 of 3	NP_003404.1	O60481-1
	ZIC3	NM_001330661.1		c.150_161delCGCCGCCGCCGC	p.Ala51_Ala54del	disruptive_inframe_deletion	Exon 1 of 3	NP_001317590.1	O60481-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZIC3	ENST00000287538.10	TSL:1 MANE Select	c.150_161delCGCCGCCGCCGC	p.Ala51_Ala54del	disruptive_inframe_deletion	Exon 1 of 3	ENSP00000287538.5	O60481-1
	ZIC3	ENST00000919832.1		c.150_161delCGCCGCCGCCGC	p.Ala51_Ala54del	disruptive_inframe_deletion	Exon 4 of 6	ENSP00000589891.1
	ZIC3	ENST00000919833.1		c.150_161delCGCCGCCGCCGC	p.Ala51_Ala54del	disruptive_inframe_deletion	Exon 4 of 6	ENSP00000589892.1

Frequencies

GnomAD3 genomes AF: 0.0000805 AC: 9 AN: 111760 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000934

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000166

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000378

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000667 AC: 70 AN: 1048866 Hom.: 0 AF XY: 0.0000644 AC XY: 22 AN XY: 341508

African (AFR) AF: 0.000120 AC: 3 AN: 25002

American (AMR) AF: 0.000106 AC: 3 AN: 28190

Ashkenazi Jewish (ASJ) AF: 0.0000536 AC: 1 AN: 18643

East Asian (EAS) AF: 0.00 AC: 0 AN: 27323

South Asian (SAS) AF: 0.0000601 AC: 3 AN: 49918

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31346

Middle Eastern (MID) AF: 0.000254 AC: 1 AN: 3940

European-Non Finnish (NFE) AF: 0.0000695 AC: 57 AN: 820176

Other (OTH) AF: 0.0000451 AC: 2 AN: 44328

GnomAD4 genome AF: 0.0000805 AC: 9 AN: 111760 Hom.: 0 Cov.: 24 AF XY: 0.0000586 AC XY: 2 AN XY: 34146

African (AFR) AF: 0.000162 AC: 5 AN: 30859

American (AMR) AF: 0.0000934 AC: 1 AN: 10712

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 3508

South Asian (SAS) AF: 0.00 AC: 0 AN: 2697

European-Finnish (FIN) AF: 0.000166 AC: 1 AN: 6008

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.0000378 AC: 2 AN: 52921

Other (OTH) AF: 0.00 AC: 0 AN: 1499

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000945

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=170/30	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs748325646; hg19: chrX-136648984;