rs16964544

Positions:

• chr19-30694432-A-G
• chr19-30694432-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001376110.1(ZNF536):​c.3896-16325A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.36 in 151,938 control chromosomes in the GnomAD database, including 10,253 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.36 (10253 hom., cov: 32)
• Consequence: ZNF536 NM_001376110.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.223

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF536	NM_001352260.2	c.*27-16325A>G		intron_variant
ZNF536	NM_001376110.1	c.3896-16325A>G		intron_variant
ZNF536	NM_001376111.1	c.3896-16325A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF536	ENST00000592773.3	c.3896-16325A>G		intron_variant		5		P1
ZNF536	ENST00000706143.1	c.1649-16325A>G		intron_variant
ZNF536	ENST00000706147.1	c.2324-16325A>G		intron_variant

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54560 AN: 151820 Hom.: 10241 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.372

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.343

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.360 AC: 54622 AN: 151938 Hom.: 10253 Cov.: 32 AF XY: 0.361 AC XY: 26772 AN XY: 74256

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.326

Gnomad4 ASJ AF: 0.372

Gnomad4 EAS AF: 0.568

Gnomad4 SAS AF: 0.390

Gnomad4 FIN AF: 0.398

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.346

Alfa AF: 0.383 Hom.: 5828

Bravo AF: 0.346

Asia WGS AF: 0.455 AC: 1584 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
DANN	Benign	0.34

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs16964544; hg19: chr19-31185339;