19-30646729-T-G

Position:

• chr19-30646729-T-G

Variant summary

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

The NM_001376110.1(ZNF536):​c.3896-64028T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.95 in 152,256 control chromosomes in the GnomAD database, including 68,988 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 0.95 (68988 hom., cov: 32)
• Consequence: ZNF536 NM_001376110.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29

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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF536	NM_001376110.1	c.3896-64028T>G		intron_variant			NP_001363039.1
ZNF536	NM_001376111.1	c.3896-64028T>G		intron_variant			NP_001363040.1
ZNF536	NM_001352260.2	c.*26+3153T>G		intron_variant			NP_001339189.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF536	ENST00000592773.3	c.3896-64028T>G		intron_variant		5		ENSP00000467909.3
ZNF536	ENST00000706148.1	c.*26+3153T>G		intron_variant				ENSP00000516231.1
ZNF536	ENST00000706150.1	c.*26+3153T>G		intron_variant				ENSP00000516233.1

Frequencies

GnomAD3 genomes AF: 0.950 AC: 144584 AN: 152138 Hom.: 68955 Cov.: 32

Gnomad AFR AF: 0.870

Gnomad AMI AF: 0.989

Gnomad AMR AF: 0.903

Gnomad ASJ AF: 0.989

Gnomad EAS AF: 0.989

Gnomad SAS AF: 0.976

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.952

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

GnomAD4 genome AF: 0.950 AC: 144670 AN: 152256 Hom.: 68988 Cov.: 32 AF XY: 0.950 AC XY: 70770 AN XY: 74460

Gnomad4 AFR AF: 0.870

Gnomad4 AMR AF: 0.903

Gnomad4 ASJ AF: 0.989

Gnomad4 EAS AF: 0.989

Gnomad4 SAS AF: 0.976

Gnomad4 FIN AF: 0.999

Gnomad4 NFE AF: 0.994

Gnomad4 OTH AF: 0.953

Alfa AF: 0.970 Hom.: 8899

Bravo AF: 0.939

Asia WGS AF: 0.967 AC: 3363 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.019
DANN	Benign	0.31

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs892095; hg19: chr19-31137636;