13-99965051-G-C

Variant names:

• chr13-99965051-G-C
• rs12869870
• NM_033132.5:c.*326C>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.*326C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00012 in 141,490 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.00011 (0 hom., cov: 24)
  • Exomes 𝑓: 0.00063 (0 hom.)
• Consequence: ZIC5 NM_033132.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.553
• Publications: 8 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=-0.85).
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency = 0.0714 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC5	NM_033132.5	c.*326C>G		3_prime_UTR_variant	Exon 2 of 2	ENST00000267294.5	NP_149123.3
ZIC5	NR_146224.1	n.2713C>G		non_coding_transcript_exon_variant	Exon 3 of 3
ZIC5	NR_146225.2	n.982C>G		non_coding_transcript_exon_variant	Exon 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIC5	ENST00000267294.5	c.*326C>G		3_prime_UTR_variant	Exon 2 of 2	1	NM_033132.5	ENSP00000267294.4

Frequencies

GnomAD3 genomes AF: 0.000114 AC: 16 AN: 139908 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00305

Gnomad SAS AF: 0.000223

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000632 AC: 1 AN: 1582 Hom.: 0 Cov.: 0 AF XY: 0.00108 AC XY: 1 AN XY: 926

African (AFR) AF: 0.00 AC: 0 AN: 8

American (AMR) AF: 0.00 AC: 0 AN: 192

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10

East Asian (EAS) AF: 0.0714 AC: 1 AN: 14

South Asian (SAS) AF: 0.00 AC: 0 AN: 74

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 6

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 832

Other (OTH) AF: 0.00 AC: 0 AN: 30

GnomAD4 genome AF: 0.000114 AC: 16 AN: 139908 Hom.: 0 Cov.: 24 AF XY: 0.000148 AC XY: 10 AN XY: 67542

African (AFR) AF: 0.00 AC: 0 AN: 36926

American (AMR) AF: 0.00 AC: 0 AN: 13892

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3416

East Asian (EAS) AF: 0.00306 AC: 15 AN: 4898

South Asian (SAS) AF: 0.000224 AC: 1 AN: 4458

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 262

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65876

Other (OTH) AF: 0.00 AC: 0 AN: 1880

Alfa AF: 0.00 Hom.: 6877

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.54
DANN	Benign	0.52
PhyloP100		0.55

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

Other links and lift over

dbSNP: rs12869870; hg19: chr13-100617305;