13-99970413-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC-TGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGCGGC

Variant names:

• chr13-99970413-T-TGGC
• rs71114653
• NM_033132.5:c.1188_1190dupGCC

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_1190dupGCC​(p.Pro397dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (181 hom., cov: 0)
  • Exomes 𝑓: 0.051 (812 hom.)
• Consequence: ZIC5 NM_033132.5 disruptive_inframe_insertion
• 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-T-TGGC is Benign according to our data. Variant chr13-99970413-T-TGGC is described in ClinVar as [Benign]. Clinvar id is 252766.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC5	NM_033132.5	c.1188_1190dupGCC	p.Pro397dup	disruptive_inframe_insertion	Exon 1 of 2	ENST00000267294.5	NP_149123.3
ZIC5	NR_146224.1	n.1494_1496dupGCC		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_1190dupGCC	p.Pro397dup	disruptive_inframe_insertion	Exon 1 of 2	1	NM_033132.5	ENSP00000267294.4
ENSG00000297638	ENST00000749511.1	n.135+319_135+321dupGGC		intron_variant	Intron 1 of 1
ENSG00000297638	ENST00000749512.1	n.104+313_104+315dupGGC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 5964 AN: 121926 Hom.: 180 Cov.: 0

Gnomad AFR AF: 0.0273

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0335

Gnomad ASJ AF: 0.0358

Gnomad EAS AF: 0.0217

Gnomad SAS AF: 0.0671

Gnomad FIN AF: 0.0701

Gnomad MID AF: 0.0563

Gnomad NFE AF: 0.0657

Gnomad OTH AF: 0.0479

GnomAD2 exomes AF: 0.00153 AC: 93 AN: 60812 AF XY: 0.00129

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00704

Gnomad NFE exome AF: 0.00165

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0505 AC: 49702 AN: 984110 Hom.: 812 Cov.: 5 AF XY: 0.0492 AC XY: 23223 AN XY: 472334

African (AFR) AF: 0.0236 AC: 423 AN: 17932

American (AMR) AF: 0.00436 AC: 28 AN: 6416

Ashkenazi Jewish (ASJ) AF: 0.0146 AC: 168 AN: 11502

East Asian (EAS) AF: 0.00671 AC: 97 AN: 14458

South Asian (SAS) AF: 0.0361 AC: 1117 AN: 30964

European-Finnish (FIN) AF: 0.00325 AC: 42 AN: 12940

Middle Eastern (MID) AF: 0.0250 AC: 71 AN: 2838

European-Non Finnish (NFE) AF: 0.0542 AC: 46190 AN: 852314

Other (OTH) AF: 0.0451 AC: 1566 AN: 34746

GnomAD4 genome AF: 0.0489 AC: 5973 AN: 122026 Hom.: 181 Cov.: 0 AF XY: 0.0485 AC XY: 2891 AN XY: 59640

African (AFR) AF: 0.0273 AC: 968 AN: 35502

American (AMR) AF: 0.0334 AC: 428 AN: 12826

Ashkenazi Jewish (ASJ) AF: 0.0358 AC: 106 AN: 2964

East Asian (EAS) AF: 0.0218 AC: 78 AN: 3586

South Asian (SAS) AF: 0.0680 AC: 246 AN: 3616

European-Finnish (FIN) AF: 0.0701 AC: 444 AN: 6338

Middle Eastern (MID) AF: 0.0507 AC: 7 AN: 138

European-Non Finnish (NFE) AF: 0.0657 AC: 3596 AN: 54728

Other (OTH) AF: 0.0516 AC: 85 AN: 1646

Alfa AF: 0.0154 Hom.: 118

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Aug 05, 2015

Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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		=73/27	polymorphism

Splicing

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: COSV57438135;