rs537713598

Variant names:

• chr15-43371012-A-C
• rs537713598
• NM_001372080.1:c.-567T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-43371012-A-C
• chr15-43371012-A-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001372080.1(ZSCAN29):​c.-567T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000022 (0 hom., cov: 28)
  • Exomes 𝑓: 0.00011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ZSCAN29 NM_001372080.1 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.879
• 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: Labcorp Genetics (formerly Invitae), G2P
• microcephaly and chorioretinopathy 1

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).

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.-567T>G		5_prime_UTR	Exon 1 of 6	NP_001359009.1	Q8IWY8-1
	TUBGCP4	NM_014444.5	MANE Select	c.-343A>C		upstream_gene	N/A	NP_055259.2
	TUBGCP4	NM_001286414.3		c.-343A>C		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.-567T>G		5_prime_UTR	Exon 1 of 6	ENSP00000507363.1	Q8IWY8-1
	ZSCAN29	ENST00000923737.1		c.-563T>G		5_prime_UTR	Exon 1 of 6	ENSP00000593796.1
	ZSCAN29	ENST00000942834.1		c.-567T>G		5_prime_UTR	Exon 1 of 5	ENSP00000612893.1

Frequencies

GnomAD3 genomes AF: 0.0000217 AC: 2 AN: 92204 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.0000277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000291

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000111 AC: 14 AN: 126480 Hom.: 0 Cov.: 0 AF XY: 0.000104 AC XY: 7 AN XY: 67278

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000375 AC: 2 AN: 5336

American (AMR) AF: 0.00 AC: 0 AN: 5578

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3654

East Asian (EAS) AF: 0.00 AC: 0 AN: 7444

South Asian (SAS) AF: 0.00 AC: 0 AN: 18192

European-Finnish (FIN) AF: 0.000143 AC: 1 AN: 6998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 600

European-Non Finnish (NFE) AF: 0.000154 AC: 11 AN: 71216

Other (OTH) AF: 0.00 AC: 0 AN: 7462

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000217 AC: 2 AN: 92316 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 44672

African (AFR) AF: 0.0000276 AC: 1 AN: 36262

American (AMR) AF: 0.00 AC: 0 AN: 7708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1980

East Asian (EAS) AF: 0.00 AC: 0 AN: 2938

South Asian (SAS) AF: 0.00 AC: 0 AN: 2534

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4728

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 178

European-Non Finnish (NFE) AF: 0.0000291 AC: 1 AN: 34336

Other (OTH) AF: 0.00 AC: 0 AN: 1274

Alfa AF: 0.000160 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	7.5
DANN	Benign	0.66
PhyloP100		-0.88
PromoterAI		0.016	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0

Splicing

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

Other links and lift over

dbSNP: rs537713598; hg19: chr15-43663210;