rs12869870

Positions:

• chr13-99965051-G-A
• chr13-99965051-G-C
• chr13-99965051-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033132.5(ZIC5):​c.*326C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 141,360 control chromosomes in the GnomAD database, including 3,465 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 (3429 hom., cov: 24)
  • Exomes 𝑓: 0.21 (36 hom.)
• Consequence: ZIC5 NM_033132.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.553

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]

ZIC5 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.226 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZIC5	NM_033132.5	c.*326C>T		3_prime_UTR_variant	2/2	ENST00000267294.5	NP_149123.3
ZIC5	NR_146224.1	n.2713C>T		non_coding_transcript_exon_variant	3/3
ZIC5	NR_146225.2	n.982C>T		non_coding_transcript_exon_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZIC5	ENST00000267294	c.*326C>T		3_prime_UTR_variant	2/2	1	NM_033132.5	ENSP00000267294.4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 31119 AN: 139784 Hom.: 3427 Cov.: 24

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.218

Gnomad ASJ AF: 0.259

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.192

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.202

GnomAD4 exome AF: 0.213 AC: 336 AN: 1576 Hom.: 36 Cov.: 0 AF XY: 0.215 AC XY: 199 AN XY: 924

Gnomad4 AFR exome AF: 0.625

Gnomad4 AMR exome AF: 0.203

Gnomad4 ASJ exome AF: 0.100

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.212

Gnomad4 NFE exome AF: 0.223

Gnomad4 OTH exome AF: 0.233

GnomAD4 genome AF: 0.223 AC: 31119 AN: 139784 Hom.: 3429 Cov.: 24 AF XY: 0.223 AC XY: 15041 AN XY: 67464

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.218

Gnomad4 ASJ AF: 0.259

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.231

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.201

Alfa AF: 0.219 Hom.: 4940

Bravo AF: 0.218

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.1
DANN	Benign	0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12869870; hg19: chr13-100617305;