rs7085530

Variant names:

• chr10-133315673-A-C
• rs7085530
• ENST00000368554.8:c.506+3832A>C

Your query was ambiguous. Multiple possible variants found:

• chr10-133315673-A-C
• chr10-133315673-A-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000368554.8(ZNF511-PRAP1):​c.506+3832A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.252 in 151,276 control chromosomes in the GnomAD database, including 5,768 homozygotes. 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 0.25 (5768 hom., cov: 29)
• Consequence: ZNF511-PRAP1 ENST00000368554.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.967
• Publications: 2 publications found

Genes affected

ZNF511-PRAP1 (HGNC:38088): (ZNF511-PRAP1 readthrough) This locus represents naturally occurring readthrough transcription between the neighboring ZNF511 (zinc finger protein 511) and PRAP1 (proline-rich acidic protein 1) genes on chromosome 10. The putative readthrough transcript may encode a fusion protein that shares sequence identity with each individual gene product and may be involved in the regulation of gene promoters, particularly those found on transfected plasmids. [provided by RefSeq, Apr 2017]

TUBGCP2 (HGNC:18599): (tubulin gamma complex component 2) Predicted to enable gamma-tubulin binding activity. Predicted to contribute to microtubule minus-end binding activity. Involved in brain development and neuron migration. Located in centrosome and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TUBGCP2 Gene-Disease associations (from GenCC):

• Norman-Roberts syndrome

  Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
• pachygyria, microcephaly, developmental delay, and dysmorphic facies, with or without seizures

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.416 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF511-PRAP1	NM_001396060.1	c.680+3832A>C		intron_variant	Intron 5 of 8		NP_001382989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF511-PRAP1	ENST00000368554.8	c.506+3832A>C		intron_variant	Intron 4 of 7	2		ENSP00000357542.5
TUBGCP2	ENST00000682123.1	c.-40+2875T>G		intron_variant	Intron 1 of 17			ENSP00000507610.1

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38092 AN: 151172 Hom.: 5750 Cov.: 29

Gnomad AFR AF: 0.421

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.0651

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.185

Gnomad OTH AF: 0.245

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.252 AC: 38138 AN: 151276 Hom.: 5768 Cov.: 29 AF XY: 0.247 AC XY: 18256 AN XY: 73860

African (AFR) AF: 0.421 AC: 17353 AN: 41212

American (AMR) AF: 0.252 AC: 3821 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 726 AN: 3466

East Asian (EAS) AF: 0.0649 AC: 334 AN: 5146

South Asian (SAS) AF: 0.176 AC: 842 AN: 4784

European-Finnish (FIN) AF: 0.152 AC: 1585 AN: 10394

Middle Eastern (MID) AF: 0.272 AC: 79 AN: 290

European-Non Finnish (NFE) AF: 0.185 AC: 12539 AN: 67792

Other (OTH) AF: 0.242 AC: 511 AN: 2108

Alfa AF: 0.226 Hom.: 569

Bravo AF: 0.266

Asia WGS AF: 0.152 AC: 529 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.5
DANN	Benign	0.14
PhyloP100		-0.97
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs7085530; hg19: chr10-135129177;