chr19-42224593-A-G

Variant names:

• chr19-42224593-A-G
• NM_133444.3:c.190A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133444.3(ZNF526):​c.190A>G​(p.Ser64Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: ZNF526 NM_133444.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.544

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06397441).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZNF526	NM_133444.3	c.190A>G	p.Ser64Gly	missense_variant	Exon 3 of 3	ENST00000301215.8	NP_597701.1
ZNF526	NM_001314033.3	c.190A>G	p.Ser64Gly	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.190A>G	p.Ser64Gly	missense_variant	Exon 3 of 3	1	NM_133444.3	ENSP00000301215.2
ENSG00000288671	ENST00000678490.1	c.91+7464T>C		intron_variant	Intron 1 of 1			ENSP00000502878.1
ZNF526	ENST00000710326.1	c.190A>G	p.Ser64Gly	missense_variant	Exon 3 of 3			ENSP00000518206.1
ZNF526	ENST00000597945.1	c.190A>G	p.Ser64Gly	missense_variant	Exon 3 of 3	4		ENSP00000473075.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.190A>G (p.S64G) alteration is located in exon 3 (coding exon 1) of the ZNF526 gene. This alteration results from a A to G substitution at nucleotide position 190, causing the serine (S) at amino acid position 64 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.95
DEOGEN2	Benign	0.039	T;T
Eigen	Benign	-0.86
Eigen_PC	Benign	-0.79
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.064	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.037
Sift	Benign	0.31	T;.
Sift4G	Benign	0.47	T;T
Polyphen		0.0	B;.
Vest4		0.19
MutPred		0.42		Loss of disorder (P = 0.0793);Loss of disorder (P = 0.0793);
MVP		0.16
MPC		0.29
ClinPred		0.064	T
GERP RS		-0.21
Varity_R		0.090
gMVP		0.15

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-42728745;