chr19-30444802-C-T

Position:

• chr19-30444802-C-T

Variant summary

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

The NM_014717.3(ZNF536):​c.1240C>T​(p.Pro414Ser) 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: 33)
• Consequence: ZNF536 NM_014717.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.28

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05929628).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF536	NM_014717.3	c.1240C>T	p.Pro414Ser	missense_variant	2/5	ENST00000355537.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF536	ENST00000355537.4	c.1240C>T	p.Pro414Ser	missense_variant	2/5	1	NM_014717.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2023

The c.1240C>T (p.P414S) alteration is located in exon 2 (coding exon 1) of the ZNF536 gene. This alteration results from a C to T substitution at nucleotide position 1240, causing the proline (P) at amino acid position 414 to be replaced by a serine (S). 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	0.072
BayesDel_addAF	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.35
DEOGEN2	Benign	0.0044	T;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.00096	T
MetaRNN	Benign	0.059	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.46	.;N
MutationTaster	Benign	0.61	D
PrimateAI	Benign	0.41	T
PROVEAN	Benign	1.9	.;N
REVEL	Benign	0.045
Sift	Benign	0.51	.;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0030	.;B
Vest4		0.14
MutPred		0.28		Gain of phosphorylation at P414 (P = 0.0285);Gain of phosphorylation at P414 (P = 0.0285);
MVP		0.043
MPC		0.81
ClinPred		0.52	D
GERP RS		4.4
Varity_R		0.048
gMVP		0.29

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: chr19-30935709;