NM_133444.3:c.1585C>T

Variant names:

• chr19-42225988-C-T
• rs587780525
• NM_133444.3:c.1585C>T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 6P and 2B. PVS1_Strong PM2 BP6_Moderate

The NM_133444.3(ZNF526):​c.1585C>T​(p.Gln529*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ZNF526 NM_133444.3 stop_gained
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.234
• Publications: 0 publications found

Genes affected

ZNF526 (HGNC:29415): (zinc finger protein 526) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000288671 (HGNC:):

GSK3A (HGNC:4616): (glycogen synthase kinase 3 alpha) This gene encodes a multifunctional Ser/Thr protein kinase that is implicated in the control of several regulatory proteins including glycogen synthase, and transcription factors, such as JUN. It also plays a role in the WNT and PI3K signaling pathways, as well as regulates the production of beta-amyloid peptides associated with Alzheimer's disease. [provided by RefSeq, Oct 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.213 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 19-42225988-C-T is Benign according to our data. Variant chr19-42225988-C-T is described in ClinVar as Benign. ClinVar VariationId is 130835.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133444.3. 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
	ZNF526	NM_133444.3	MANE Select	c.1585C>T	p.Gln529*	stop_gained	Exon 3 of 3	NP_597701.1	H9ZYJ3
	ZNF526	NM_001314033.3		c.1585C>T	p.Gln529*	stop_gained	Exon 3 of 3	NP_001300962.1	H9ZYJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF526	ENST00000301215.8	TSL:1 MANE Select	c.1585C>T	p.Gln529*	stop_gained	Exon 3 of 3	ENSP00000301215.2	Q8TF50
	ENSG00000288671	ENST00000678490.1		c.91+6069G>A		intron	N/A	ENSP00000502878.1	A0A7I2V2F5
	ZNF526	ENST00000710326.1		c.1585C>T	p.Gln529*	stop_gained	Exon 3 of 3	ENSP00000518206.1	Q8TF50

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.52	D
BayesDel_noAF	Pathogenic	0.51
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Benign	0.46	N
PhyloP100		-0.23
Vest4		0.068
GERP RS		4.8
Mutation Taster		=27/173	disease causing

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: rs587780525; hg19: chr19-42730140;