19-30443835-G-C

Position:

• chr19-30443835-G-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_014717.3(ZNF536):​c.273G>C​(p.Glu91Asp) 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 Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF536 NM_014717.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.194

Genes affected

ZNF536 (HGNC:29025): (zinc finger protein 536) The protein encoded by this gene is a highly conserved zinc finger protein. The encoded protein is most abundant in brain, where it negatively regulates neuronal differentiation. [provided by RefSeq, Sep 2015]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.037659407).
• BP6: Variant 19-30443835-G-C is Benign according to our data. Variant chr19-30443835-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 2534795.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF536	NM_014717.3	c.273G>C	p.Glu91Asp	missense_variant	2/5	ENST00000355537.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF536	ENST00000355537.4	c.273G>C	p.Glu91Asp	missense_variant	2/5	1	NM_014717.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 07, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	6.3
DANN	Benign	0.19
DEOGEN2	Benign	0.0052	T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.038	T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-0.34	.;.;N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.47	T
PROVEAN	Benign	0.23	.;.;N
REVEL	Benign	0.079
Sift	Benign	1.0	.;.;T
Sift4G	Benign	0.78	T;T;T
Polyphen		0.0	.;.;B
Vest4		0.13
MutPred		0.24		Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);Gain of relative solvent accessibility (P = 0.1894);
MVP		0.043
MPC		0.71
ClinPred		0.044	T
GERP RS		-11
Varity_R		0.083
gMVP		0.18

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: chr19-30934742;