chr15-43370975-A-ACCCCGGCCCCGG

Position:

• chr15-43370975-A-ACCCCGGCCCCGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001372080.1(ZSCAN29):​c.-531_-530insCCGGGGCCGGGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (5099 hom., cov: 0)
  • Exomes 𝑓: 0.26 (4216 hom.)
• Consequence: ZSCAN29 NM_001372080.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.691

Genes affected

ZSCAN29 (HGNC:26673): (zinc finger and SCAN domain containing 29) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

TUBGCP4 (HGNC:16691): (tubulin gamma complex component 4) This gene encodes a component of the gamma-tubulin ring complex, which is required for microtubule nucleation. In mammalian cells, the protein localizes to centrosomes in association with gamma-tubulin. Crystal structure analysis revealed a structure composed of five helical bundles arranged around conserved hydrophobic cores. An exposed surface area located in the C-terminal domain is essential and sufficient for direct binding to gamma-tubulin. Mutations in this gene that alter microtubule organization are associated with microcephaly and chorioretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2015]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-43370975-A-ACCCCGGCCCCGG is Benign according to our data. Variant chr15-43370975-A-ACCCCGGCCCCGG is described in ClinVar as [Benign]. Clinvar id is 1242749.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.346 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSCAN29	NM_001372080.1	c.-531_-530insCCGGGGCCGGGG		5_prime_UTR_variant	1/6	ENST00000684362.1
ZSCAN29	XM_047432187.1	c.-851_-850insCCGGGGCCGGGG		5_prime_UTR_variant	1/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSCAN29	ENST00000684362.1	c.-531_-530insCCGGGGCCGGGG		5_prime_UTR_variant	1/6		NM_001372080.1	P1
TUBGCP4	ENST00000570081.1	n.293+1293_293+1304dup		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.233 AC: 34967 AN: 150378 Hom.: 5090 Cov.: 0

Gnomad AFR AF: 0.0594

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.354

Gnomad ASJ AF: 0.262

Gnomad EAS AF: 0.286

Gnomad SAS AF: 0.257

Gnomad FIN AF: 0.334

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.286

Gnomad OTH AF: 0.252

GnomAD4 exome AF: 0.259 AC: 28088 AN: 108502 Hom.: 4216 Cov.: 0 AF XY: 0.257 AC XY: 15073 AN XY: 58564

Gnomad4 AFR exome AF: 0.0377

Gnomad4 AMR exome AF: 0.347

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.248

Gnomad4 SAS exome AF: 0.228

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.269

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.232 AC: 34985 AN: 150494 Hom.: 5099 Cov.: 0 AF XY: 0.239 AC XY: 17521 AN XY: 73412

Gnomad4 AFR AF: 0.0592

Gnomad4 AMR AF: 0.354

Gnomad4 ASJ AF: 0.262

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.334

Gnomad4 NFE AF: 0.286

Gnomad4 OTH AF: 0.252

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11279953; hg19: chr15-43663173;