rs12869870

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000267294.5(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
ENST00000267294.5 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.553
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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
ZIC5NM_033132.5 linkuse as main transcriptc.*326C>T 3_prime_UTR_variant 2/2 ENST00000267294.5 NP_149123.3
ZIC5NR_146224.1 linkuse as main transcriptn.2713C>T non_coding_transcript_exon_variant 3/3
ZIC5NR_146225.2 linkuse as main transcriptn.982C>T non_coding_transcript_exon_variant 2/2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZIC5ENST00000267294.5 linkuse as main transcriptc.*326C>T 3_prime_UTR_variant 2/21 NM_033132.5 ENSP00000267294 P1

Frequencies

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs12869870; hg19: chr13-100617305; API