13-99962942-G-C

Variant names:

• chr13-99962942-G-C
• rs3742253
• NM_033132.5:c.*2435C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033132.5(ZIC5):​c.*2435C>G variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,088 control chromosomes in the GnomAD database, including 3,613 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (3613 hom., cov: 33)
  • Failed GnomAD Quality Control
• Consequence: ZIC5 NM_033132.5 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.271 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC5	NM_033132.5	c.*2435C>G		downstream_gene_variant		ENST00000267294.5	NP_149123.3
ZIC5	NR_146224.1	n.*22C>G		downstream_gene_variant
ZIC5	NR_146225.2	n.*22C>G		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIC5	ENST00000267294.5	c.*2435C>G		downstream_gene_variant		1	NM_033132.5	ENSP00000267294.4

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32847 AN: 151980 Hom.: 3605 Cov.: 33

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.261

Gnomad AMR AF: 0.277

Gnomad ASJ AF: 0.253

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.202

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.216 AC: 32887 AN: 152088 Hom.: 3613 Cov.: 33 AF XY: 0.217 AC XY: 16137 AN XY: 74332

African (AFR) AF: 0.208 AC: 8617 AN: 41496

American (AMR) AF: 0.278 AC: 4242 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 879 AN: 3468

East Asian (EAS) AF: 0.116 AC: 603 AN: 5184

South Asian (SAS) AF: 0.207 AC: 1001 AN: 4826

European-Finnish (FIN) AF: 0.202 AC: 2132 AN: 10560

Middle Eastern (MID) AF: 0.194 AC: 57 AN: 294

European-Non Finnish (NFE) AF: 0.216 AC: 14694 AN: 67988

Other (OTH) AF: 0.202 AC: 424 AN: 2096

Alfa AF: 0.221 Hom.: 498

Bravo AF: 0.226

Asia WGS AF: 0.166 AC: 570 AN: 3452

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.1
DANN	Benign	0.55
PhyloP100		-0.18

Splicing

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

Other links and lift over

dbSNP: rs3742253; hg19: chr13-100615196;