chr13-99970413-TGGCGGCGGCGGC-T

Position:

• chr13-99970413-TGGCGGCGGCGGC-T

Variant summary

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

The NM_033132.5(ZIC5):​c.1179_1190del​(p.Pro397_Pro400del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00423 in 1,106,504 control chromosomes in the GnomAD database, including 174 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0039 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0043 (174 hom.)
• Consequence: ZIC5 NM_033132.5 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56

Genes affected

ZIC5 (HGNC:20322): (Zic family member 5) This gene encodes a member of the ZIC family of C2H2-type zinc finger proteins. The encoded protein may act as a transcriptional repressor. Studies in mouse and Xenopus support a role for this gene in neural crest development. Elevated expression of this gene has been observed in various human cancers and may contribute to cancer progression. This gene is closely linked to a related family member on chromosome 13. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_033132.5
• BS2: High AC in GnomAd4 at 478 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZIC5	NM_033132.5	c.1179_1190del	p.Pro397_Pro400del	inframe_deletion	1/2	ENST00000267294.5	NP_149123.3
ZIC5	NR_146224.1	n.1485_1496del		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZIC5	ENST00000267294.5	c.1179_1190del	p.Pro397_Pro400del	inframe_deletion	1/2	1	NM_033132.5	ENSP00000267294	P1

Frequencies

GnomAD3 genomes AF: 0.00391 AC: 477 AN: 121978 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00503

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00359

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00501

Gnomad SAS AF: 0.00495

Gnomad FIN AF: 0.000789

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00361

Gnomad OTH AF: 0.00491

GnomAD3 exomes AF: 0.000608 AC: 37 AN: 60812 Hom.: 1 AF XY: 0.000673 AC XY: 25 AN XY: 37140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000329

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000342

Gnomad FIN exome AF: 0.000556

Gnomad NFE exome AF: 0.000842

Gnomad OTH exome AF: 0.00158

GnomAD4 exome AF: 0.00427 AC: 4202 AN: 984426 Hom.: 174 AF XY: 0.00429 AC XY: 2028 AN XY: 472502

Gnomad4 AFR exome AF: 0.00485

Gnomad4 AMR exome AF: 0.00390

Gnomad4 ASJ exome AF: 0.000870

Gnomad4 EAS exome AF: 0.00333

Gnomad4 SAS exome AF: 0.00274

Gnomad4 FIN exome AF: 0.00301

Gnomad4 NFE exome AF: 0.00433

Gnomad4 OTH exome AF: 0.00598

GnomAD4 genome AF: 0.00392 AC: 478 AN: 122078 Hom.: 0 Cov.: 0 AF XY: 0.00374 AC XY: 223 AN XY: 59662

Gnomad4 AFR AF: 0.00504

Gnomad4 AMR AF: 0.00359

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00502

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.000789

Gnomad4 NFE AF: 0.00362

Gnomad4 OTH AF: 0.00486

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: rs71114653; hg19: chr13-100622667;