19-30444312-C-G

Position:

• chr19-30444312-C-G

Variant summary

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

The NM_014717.3(ZNF536):​c.750C>G​(p.Asp250Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,433,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ZNF536 NM_014717.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00100

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 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=0.075262666).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF536	NM_014717.3	c.750C>G	p.Asp250Glu	missense_variant	2/5	ENST00000355537.4	NP_055532.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF536	ENST00000355537.4	c.750C>G	p.Asp250Glu	missense_variant	2/5	1	NM_014717.3	ENSP00000347730.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000140 AC: 2 AN: 1433408 Hom.: 0 Cov.: 33 AF XY: 0.00000140 AC XY: 1 AN XY: 712356

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: 0.00

Gnomad4 NFE exome AF: 0.00000181

Gnomad4 OTH exome AF: 0.00

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

Nov 13, 2024

The c.750C>G (p.D250E) alteration is located in exon 2 (coding exon 1) of the ZNF536 gene. This alteration results from a C to G substitution at nucleotide position 750, causing the aspartic acid (D) at amino acid position 250 to be replaced by a glutamic acid (E). 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	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.50
DANN	Benign	0.64
DEOGEN2	Benign	0.014	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.075	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	1.4	.;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.3	.;N
REVEL	Benign	0.22
Sift	Benign	0.22	.;T
Sift4G	Benign	0.60	T;T
Polyphen		0.84	.;P
Vest4		0.27
MutPred		0.17		Loss of glycosylation at S247 (P = 0.164);Loss of glycosylation at S247 (P = 0.164);
MVP		0.23
MPC		1.8
ClinPred		0.69	D
GERP RS		-0.14
Varity_R		0.060
gMVP		0.30

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: chr19-30935219;