19-30345341-A-G

Position:

• chr19-30345341-A-G

Variant summary

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

The NM_001376110.1(ZNF536):​c.-3+61200A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,170 control chromosomes in the GnomAD database, including 30,356 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 0.62 (30356 hom., cov: 33)
• Consequence: ZNF536 NM_001376110.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.352

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.788 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF536	NM_001376110.1	c.-3+61200A>G		intron_variant			NP_001363039.1
ZNF536	NM_001376111.1	c.-3+61200A>G		intron_variant			NP_001363040.1
ZNF536	XM_011527554.3	c.-119-7027A>G		intron_variant			XP_011525856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF536	ENST00000585628.5	c.-119-7027A>G		intron_variant		5		ENSP00000465771
ZNF536	ENST00000591488.1	c.-119-7027A>G		intron_variant		3		ENSP00000465268
ZNF536	ENST00000592773.3	c.-3+61200A>G		intron_variant		5		ENSP00000467909	P1

Frequencies

GnomAD3 genomes AF: 0.624 AC: 94816 AN: 152052 Hom.: 30340 Cov.: 33

Gnomad AFR AF: 0.739

Gnomad AMI AF: 0.632

Gnomad AMR AF: 0.675

Gnomad ASJ AF: 0.542

Gnomad EAS AF: 0.808

Gnomad SAS AF: 0.690

Gnomad FIN AF: 0.527

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.624

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

GnomAD4 genome AF: 0.623 AC: 94876 AN: 152170 Hom.: 30356 Cov.: 33 AF XY: 0.624 AC XY: 46458 AN XY: 74406

Gnomad4 AFR AF: 0.739

Gnomad4 AMR AF: 0.676

Gnomad4 ASJ AF: 0.542

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.527

Gnomad4 NFE AF: 0.542

Gnomad4 OTH AF: 0.628

Alfa AF: 0.562 Hom.: 47078

Bravo AF: 0.640

Asia WGS AF: 0.735 AC: 2554 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1019937; hg19: chr19-30836248;