NM_001372080.1:c.-567T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001372080.1(ZSCAN29):​c.-567T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00325 in 218,784 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0066 (3 hom., cov: 28)
  • Exomes 𝑓: 0.00081 (1 hom.)
• Consequence: ZSCAN29 NM_001372080.1 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 15-43371012-A-G is Benign according to our data. Variant chr15-43371012-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1196047.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

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

Frequencies

GnomAD3 genomes AF: 0.00660 AC: 608 AN: 92186 Hom.: 3 Cov.: 28

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.00265

Gnomad AMR AF: 0.00442

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: 0.000116

Gnomad OTH AF: 0.00556

GnomAD4 exome AF: 0.000814 AC: 103 AN: 126486 Hom.: 1 Cov.: 0 AF XY: 0.000654 AC XY: 44 AN XY: 67274

African (AFR) AF: 0.0144 AC: 77 AN: 5334

American (AMR) AF: 0.00125 AC: 7 AN: 5582

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 7448

South Asian (SAS) AF: 0.0000550 AC: 1 AN: 18182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7002

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

European-Non Finnish (NFE) AF: 0.000112 AC: 8 AN: 71216

Other (OTH) AF: 0.00134 AC: 10 AN: 7468

GnomAD4 genome AF: 0.00659 AC: 608 AN: 92298 Hom.: 3 Cov.: 28 AF XY: 0.00609 AC XY: 272 AN XY: 44656

African (AFR) AF: 0.0155 AC: 562 AN: 36262

American (AMR) AF: 0.00441 AC: 34 AN: 7706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1978

East Asian (EAS) AF: 0.00 AC: 0 AN: 2936

South Asian (SAS) AF: 0.00 AC: 0 AN: 2532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4724

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

European-Non Finnish (NFE) AF: 0.000117 AC: 4 AN: 34330

Other (OTH) AF: 0.00549 AC: 7 AN: 1274

Alfa AF: 0.000585 Hom.: 0

Bravo AF: 0.00469

ClinVar

ClinVar submissions as Germline

Significance: Likely 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
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.4
DANN	Benign	0.66
PhyloP100		-0.88
PromoterAI		0.20	Neutral

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;