rs16964420

Positions:

• chr19-30619326-G-A

Variant summary

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

The NM_001376110.1(ZNF536):​c.3895+69812G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,906 control chromosomes in the GnomAD database, including 8,655 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 0.33 (8655 hom., cov: 32)
• Consequence: ZNF536 NM_001376110.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.334

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.468 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF536	NM_001352260.2	c.3896-24211G>A		intron_variant			NP_001339189.1
ZNF536	NM_001376110.1	c.3895+69812G>A		intron_variant			NP_001363039.1
ZNF536	NM_001376111.1	c.3895+69812G>A		intron_variant			NP_001363040.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF536	ENST00000592773.3	c.3895+69812G>A		intron_variant		5		ENSP00000467909	P1
ZNF536	ENST00000706143.1	c.1648+69812G>A		intron_variant				ENSP00000516227
ZNF536	ENST00000706147.1	c.2323+84327G>A		intron_variant				ENSP00000516230

Frequencies

GnomAD3 genomes AF: 0.326 AC: 49557 AN: 151786 Hom.: 8645 Cov.: 32

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.483

Gnomad SAS AF: 0.399

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.333

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.326 AC: 49588 AN: 151906 Hom.: 8655 Cov.: 32 AF XY: 0.333 AC XY: 24701 AN XY: 74186

Gnomad4 AFR AF: 0.223

Gnomad4 AMR AF: 0.406

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.484

Gnomad4 SAS AF: 0.398

Gnomad4 FIN AF: 0.467

Gnomad4 NFE AF: 0.333

Gnomad4 OTH AF: 0.330

Alfa AF: 0.333 Hom.: 11790

Bravo AF: 0.316

Asia WGS AF: 0.462 AC: 1606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.41
DANN	Benign	0.53

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs16964420; hg19: chr19-31110233;