chr13-99970413-TGGCGGCGGCGGCGGC-T

Variant names:

• chr13-99970413-TGGCGGCGGCGGCGGC-T
• rs71114653
• NM_033132.5:c.1176_1190delGCCGCCGCCGCCGCC

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP3 BP6_Moderate BS2

The NM_033132.5(ZIC5):​c.1176_1190delGCCGCCGCCGCCGCC​(p.Pro393_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 0.0101 in 1,106,574 control chromosomes in the GnomAD database, including 1,047 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0072 (9 hom., cov: 0)
  • Exomes 𝑓: 0.010 (1038 hom.)
• Consequence: ZIC5 NM_033132.5 disruptive_inframe_deletion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -7 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_033132.5
• BP6: Variant 13-99970413-TGGCGGCGGCGGCGGC-T is Benign according to our data. Variant chr13-99970413-TGGCGGCGGCGGCGGC-T is described in ClinVar as [Likely_benign]. Clinvar id is 787178.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 883 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZIC5	NM_033132.5	c.1176_1190delGCCGCCGCCGCCGCC	p.Pro393_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	ENST00000267294.5	NP_149123.3
ZIC5	NR_146224.1	n.1482_1496delGCCGCCGCCGCCGCC		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.1176_1190delGCCGCCGCCGCCGCC	p.Pro393_Pro397del	disruptive_inframe_deletion	Exon 1 of 2	1	NM_033132.5	ENSP00000267294.4
ENSG00000297638	ENST00000749511.1	n.135+307_135+321delGGCGGCGGCGGCGGC		intron_variant	Intron 1 of 1
ENSG00000297638	ENST00000749512.1	n.104+301_104+315delGGCGGCGGCGGCGGC		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00725 AC: 884 AN: 121968 Hom.: 9 Cov.: 0

Gnomad AFR AF: 0.00251

Gnomad AMI AF: 0.0529

Gnomad AMR AF: 0.00789

Gnomad ASJ AF: 0.000675

Gnomad EAS AF: 0.00111

Gnomad SAS AF: 0.00275

Gnomad FIN AF: 0.00489

Gnomad MID AF: 0.0352

Gnomad NFE AF: 0.0108

Gnomad OTH AF: 0.00736

GnomAD2 exomes AF: 0.00322 AC: 196 AN: 60812 AF XY: 0.00310

Gnomad AFR exome AF: 0.00125

Gnomad AMR exome AF: 0.00230

Gnomad ASJ exome AF: 0.000264

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00426

Gnomad NFE exome AF: 0.00449

Gnomad OTH exome AF: 0.00711

GnomAD4 exome AF: 0.0104 AC: 10261 AN: 984506 Hom.: 1038 AF XY: 0.0108 AC XY: 5110 AN XY: 472550

African (AFR) AF: 0.00212 AC: 38 AN: 17928

American (AMR) AF: 0.00545 AC: 35 AN: 6422

Ashkenazi Jewish (ASJ) AF: 0.000956 AC: 11 AN: 11504

East Asian (EAS) AF: 0.000622 AC: 9 AN: 14458

South Asian (SAS) AF: 0.00481 AC: 149 AN: 30964

European-Finnish (FIN) AF: 0.0191 AC: 248 AN: 12956

Middle Eastern (MID) AF: 0.0120 AC: 34 AN: 2840

European-Non Finnish (NFE) AF: 0.0109 AC: 9331 AN: 852680

Other (OTH) AF: 0.0117 AC: 406 AN: 34754

GnomAD4 genome AF: 0.00723 AC: 883 AN: 122068 Hom.: 9 Cov.: 0 AF XY: 0.00642 AC XY: 383 AN XY: 59656

African (AFR) AF: 0.00251 AC: 89 AN: 35514

American (AMR) AF: 0.00780 AC: 100 AN: 12826

Ashkenazi Jewish (ASJ) AF: 0.000675 AC: 2 AN: 2964

East Asian (EAS) AF: 0.00112 AC: 4 AN: 3586

South Asian (SAS) AF: 0.00277 AC: 10 AN: 3614

European-Finnish (FIN) AF: 0.00489 AC: 31 AN: 6338

Middle Eastern (MID) AF: 0.0362 AC: 5 AN: 138

European-Non Finnish (NFE) AF: 0.0108 AC: 594 AN: 54762

Other (OTH) AF: 0.00729 AC: 12 AN: 1646

Alfa AF: 0.00309 Hom.: 118

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Dec 07, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.6
Mutation Taster		=198/2	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;