19-30443816-C-A

Position:

• chr19-30443816-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014717.3(ZNF536):​c.254C>A​(p.Ala85Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ZNF536 NM_014717.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.97

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]

ZNF536 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3466947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF536	NM_014717.3	c.254C>A	p.Ala85Asp	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.254C>A	p.Ala85Asp	missense_variant	2/5	1	NM_014717.3	ENSP00000347730.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460830 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726736

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: 8.99e-7

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

Feb 15, 2023

The c.254C>A (p.A85D) alteration is located in exon 2 (coding exon 1) of the ZNF536 gene. This alteration results from a C to A substitution at nucleotide position 254, causing the alanine (A) at amino acid position 85 to be replaced by an aspartic acid (D). 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	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.096	D
BayesDel_noAF	Benign	-0.10
CADD	Pathogenic	31
DANN	Uncertain	0.99
DEOGEN2	Benign	0.023	T;.;T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.91	D;D;D
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-1.2	T
MutationAssessor	Benign	0.46	.;.;N
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.5	.;.;N
REVEL	Benign	0.24
Sift	Uncertain	0.0010	.;.;D
Sift4G	Uncertain	0.0070	D;D;D
Polyphen		1.0	.;.;D
Vest4		0.84
MutPred		0.33		Loss of MoRF binding (P = 0.1144);Loss of MoRF binding (P = 0.1144);Loss of MoRF binding (P = 0.1144);
MVP		0.14
MPC		2.3
ClinPred		0.80	D
GERP RS		5.5
Varity_R		0.63
gMVP		0.78

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: chr19-30934723;