chr13-99970413-TGGCGGCGGC-T

Position:

• chr13-99970413-TGGCGGCGGC-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP3 BS1 BS2

The NM_033132.5(ZIC5):​c.1182_1190del​(p.Pro398_Pro400del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00908 in 1,106,596 control chromosomes in the GnomAD database, including 307 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.010 (9 hom., cov: 0)
  • Exomes 𝑓: 0.0089 (298 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 Benign. Variant got -9 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_033132.5
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0102 (1248/122066) while in subpopulation EAS AF= 0.0441 (158/3584). AF 95% confidence interval is 0.0385. There are 9 homozygotes in gnomad4. There are 621 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1248 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZIC5	NM_033132.5	c.1182_1190del	p.Pro398_Pro400del	inframe_deletion	1/2	ENST00000267294.5	NP_149123.3
ZIC5	NR_146224.1	n.1488_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.1182_1190del	p.Pro398_Pro400del	inframe_deletion	1/2	1	NM_033132.5	ENSP00000267294	P1

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1249 AN: 121966 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.00536

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0167

Gnomad ASJ AF: 0.0280

Gnomad EAS AF: 0.0442

Gnomad SAS AF: 0.00660

Gnomad FIN AF: 0.00205

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00986

Gnomad OTH AF: 0.0160

GnomAD3 exomes AF: 0.00109 AC: 66 AN: 60812 Hom.: 1 AF XY: 0.00121 AC XY: 45 AN XY: 37140

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00164

Gnomad ASJ exome AF: 0.00211

Gnomad EAS exome AF: 0.000515

Gnomad SAS exome AF: 0.000512

Gnomad FIN exome AF: 0.000185

Gnomad NFE exome AF: 0.00140

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00894 AC: 8797 AN: 984530 Hom.: 298 AF XY: 0.00912 AC XY: 4309 AN XY: 472552

Gnomad4 AFR exome AF: 0.00424

Gnomad4 AMR exome AF: 0.0125

Gnomad4 ASJ exome AF: 0.0207

Gnomad4 EAS exome AF: 0.0350

Gnomad4 SAS exome AF: 0.00346

Gnomad4 FIN exome AF: 0.00100

Gnomad4 NFE exome AF: 0.00867

Gnomad4 OTH exome AF: 0.0104

GnomAD4 genome AF: 0.0102 AC: 1248 AN: 122066 Hom.: 9 Cov.: 0 AF XY: 0.0104 AC XY: 621 AN XY: 59656

Gnomad4 AFR AF: 0.00535

Gnomad4 AMR AF: 0.0167

Gnomad4 ASJ AF: 0.0280

Gnomad4 EAS AF: 0.0441

Gnomad4 SAS AF: 0.00636

Gnomad4 FIN AF: 0.00205

Gnomad4 NFE AF: 0.00986

Gnomad4 OTH AF: 0.0164

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;