19-42224798-G-T

Variant names:

• chr19-42224798-G-T
• rs146635897
• NM_133444.3:c.395G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_133444.3(ZNF526):​c.395G>T​(p.Arg132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: ZNF526 NM_133444.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.146

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:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09668106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF526	NM_133444.3	c.395G>T	p.Arg132Leu	missense_variant	Exon 3 of 3	ENST00000301215.8	NP_597701.1
ZNF526	NM_001314033.3	c.395G>T	p.Arg132Leu	missense_variant	Exon 3 of 3		NP_001300962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZNF526	ENST00000301215.8	c.395G>T	p.Arg132Leu	missense_variant	Exon 3 of 3	1	NM_133444.3	ENSP00000301215.2
ENSG00000288671	ENST00000678490.1	c.91+7259C>A		intron_variant	Intron 1 of 1			ENSP00000502878.1
ZNF526	ENST00000710326.1	c.395G>T	p.Arg132Leu	missense_variant	Exon 3 of 3			ENSP00000518206.1
ZNF526	ENST00000597945.1	c.*189G>T		downstream_gene_variant		4		ENSP00000473075.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000199 AC: 5 AN: 251206 Hom.: 0 AF XY: 0.0000368 AC XY: 5 AN XY: 135792

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000440

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461656 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727120

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.00000629

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ExAC AF: 0.0000412 AC: 5

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.94
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Uncertain	2.1	M
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.045
Sift	Benign	0.096	T
Sift4G	Benign	0.22	T
Polyphen		0.20	B
Vest4		0.26
MutPred		0.56		Loss of disorder (P = 0.0678);
MVP		0.13
MPC		0.46
ClinPred		0.11	T
GERP RS		-1.2
Varity_R		0.085
gMVP		0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs146635897; hg19: chr19-42728950;