chr15-43370975-ACCCCGG-A

Variant names:

• chr15-43370975-ACCCCGG-A
• rs11279953
• NM_001372080.1:c.-536_-531delCCGGGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001372080.1(ZSCAN29):​c.-536_-531delCCGGGG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 258,998 control chromosomes in the GnomAD database, including 27,986 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.45 (18533 hom., cov: 0)
  • Exomes 𝑓: 0.41 (9453 hom.)
• Consequence: ZSCAN29 NM_001372080.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.691
• Publications: 0 publications found

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]

TUBGCP4 Gene-Disease associations (from GenCC):

• microcephaly and chorioretinopathy 3

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• microcephaly and chorioretinopathy 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 15-43370975-ACCCCGG-A is Benign according to our data. Variant chr15-43370975-ACCCCGG-A is described in ClinVar as Benign. ClinVar VariationId is 1240667.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001372080.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN29	NM_001372080.1	MANE Select	c.-536_-531delCCGGGG		5_prime_UTR	Exon 1 of 6	NP_001359009.1	Q8IWY8-1
	TUBGCP4	NM_014444.5	MANE Select	c.-379_-374delCCCCGG		upstream_gene	N/A	NP_055259.2
	TUBGCP4	NM_001286414.3		c.-379_-374delCCCCGG		upstream_gene	N/A	NP_001273343.1	Q9UGJ1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN29	ENST00000684362.1	MANE Select	c.-536_-531delCCGGGG		5_prime_UTR	Exon 1 of 6	ENSP00000507363.1	Q8IWY8-1
	ZSCAN29	ENST00000942835.1		c.-536_-531delCCGGGG		5_prime_UTR	Exon 1 of 6	ENSP00000612894.1
	ZSCAN29	ENST00000923737.1		c.-532_-527delCCGGGG		5_prime_UTR	Exon 1 of 6	ENSP00000593796.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 66867 AN: 150360 Hom.: 18476 Cov.: 0

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.398

Gnomad EAS AF: 0.474

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.413

GnomAD4 exome AF: 0.407 AC: 44152 AN: 108522 Hom.: 9453 AF XY: 0.414 AC XY: 24262 AN XY: 58562

African (AFR) AF: 0.828 AC: 2682 AN: 3238

American (AMR) AF: 0.415 AC: 2221 AN: 5354

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 1197 AN: 2610

East Asian (EAS) AF: 0.582 AC: 2813 AN: 4834

South Asian (SAS) AF: 0.506 AC: 9327 AN: 18434

European-Finnish (FIN) AF: 0.260 AC: 1450 AN: 5580

Middle Eastern (MID) AF: 0.452 AC: 199 AN: 440

European-Non Finnish (NFE) AF: 0.352 AC: 21865 AN: 62062

Other (OTH) AF: 0.402 AC: 2398 AN: 5970

GnomAD4 genome AF: 0.445 AC: 66974 AN: 150476 Hom.: 18533 Cov.: 0 AF XY: 0.439 AC XY: 32208 AN XY: 73394

African (AFR) AF: 0.783 AC: 32269 AN: 41200

American (AMR) AF: 0.357 AC: 5420 AN: 15184

Ashkenazi Jewish (ASJ) AF: 0.398 AC: 1377 AN: 3462

East Asian (EAS) AF: 0.474 AC: 2350 AN: 4962

South Asian (SAS) AF: 0.443 AC: 2089 AN: 4716

European-Finnish (FIN) AF: 0.211 AC: 2185 AN: 10366

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20073 AN: 67320

Other (OTH) AF: 0.416 AC: 867 AN: 2084

Alfa AF: 0.234 Hom.: 276

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.69
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11279953; hg19: chr15-43663173;