chr13-99970413-TGGC-T

Variant names:

• chr13-99970413-TGGC-T
• rs71114653
• NM_033132.5:c.1188_1190delGCC

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP3 BP6_Very_Strong BA1

The NM_033132.5(ZIC5):​c.1188_1190delGCC​(p.Pro397del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,099,906 control chromosomes in the GnomAD database, including 26,305 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (10159 hom., cov: 0)
  • Exomes 𝑓: 0.18 (16146 hom.)
• Consequence: ZIC5 NM_033132.5 disruptive_inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.56
• Publications: 9 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]

ENSG00000297638 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_033132.5
• BP6: Variant 13-99970413-TGGC-T is Benign according to our data. Variant chr13-99970413-TGGC-T is described in ClinVar as [Benign]. Clinvar id is 403621.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.659 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC5	NM_033132.5	c.1188_1190delGCC	p.Pro397del	disruptive_inframe_deletion	Exon 1 of 2	ENST00000267294.5	NP_149123.3
ZIC5	NR_146224.1	n.1494_1496delGCC		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZIC5	ENST00000267294.5	c.1188_1190delGCC	p.Pro397del	disruptive_inframe_deletion	Exon 1 of 2	1	NM_033132.5	ENSP00000267294.4
ENSG00000297638	ENST00000749511.1	n.135+319_135+321delGGC		intron_variant	Intron 1 of 1
ENSG00000297638	ENST00000749512.1	n.104+313_104+315delGGC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.372 AC: 45311 AN: 121798 Hom.: 10139 Cov.: 0

Gnomad AFR AF: 0.666

Gnomad AMI AF: 0.310

Gnomad AMR AF: 0.339

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.245

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.320

GnomAD2 exomes AF: 0.0131 AC: 796 AN: 60812 AF XY: 0.0114

Gnomad AFR exome AF: 0.00810

Gnomad AMR exome AF: 0.00296

Gnomad ASJ exome AF: 0.00528

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0457

Gnomad NFE exome AF: 0.0148

Gnomad OTH exome AF: 0.00632

GnomAD4 exome AF: 0.180 AC: 176352 AN: 978006 Hom.: 16146 AF XY: 0.177 AC XY: 82953 AN XY: 469078

African (AFR) AF: 0.563 AC: 10069 AN: 17888

American (AMR) AF: 0.0894 AC: 568 AN: 6354

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 1356 AN: 11434

East Asian (EAS) AF: 0.0643 AC: 923 AN: 14356

South Asian (SAS) AF: 0.135 AC: 4168 AN: 30834

European-Finnish (FIN) AF: 0.0549 AC: 705 AN: 12852

Middle Eastern (MID) AF: 0.141 AC: 397 AN: 2808

European-Non Finnish (NFE) AF: 0.179 AC: 151793 AN: 846980

Other (OTH) AF: 0.185 AC: 6373 AN: 34500

GnomAD4 genome AF: 0.372 AC: 45384 AN: 121900 Hom.: 10159 Cov.: 0 AF XY: 0.371 AC XY: 22088 AN XY: 59580

African (AFR) AF: 0.666 AC: 23620 AN: 35460

American (AMR) AF: 0.340 AC: 4345 AN: 12794

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 797 AN: 2962

East Asian (EAS) AF: 0.246 AC: 878 AN: 3576

South Asian (SAS) AF: 0.278 AC: 1004 AN: 3612

European-Finnish (FIN) AF: 0.238 AC: 1506 AN: 6326

Middle Eastern (MID) AF: 0.346 AC: 47 AN: 136

European-Non Finnish (NFE) AF: 0.228 AC: 12453 AN: 54708

Other (OTH) AF: 0.318 AC: 523 AN: 1646

Alfa AF: 0.0900 Hom.: 118

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=83/17	polymorphism (auto)

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: rs71114653; hg19: chr13-100622667; COSMIC: COSV57437067;