rs10518268

chr19-30582097-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001376110.1(ZNF536):c.3895+32583G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0111 in 152,258 control chromosomes in the GnomAD database, including 15 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 0.011 (15 hom., cov: 32)
• Consequence: ZNF536 NM_001376110.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14

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=-0.91).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0111 (1694/152258) while in subpopulation NFE AF= 0.0189 (1284/68016). AF 95% confidence interval is 0.018. There are 15 homozygotes in gnomad4. There are 769 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1694 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZNF536	NM_001352260.2	c.3895+32583G>C		intron_variant
ZNF536	NM_001376110.1	c.3895+32583G>C		intron_variant
ZNF536	NM_001376111.1	c.3895+32583G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF536	ENST00000592773.3	c.3895+32583G>C		intron_variant		5		P1
ZNF536	ENST00000706143.1	c.1648+32583G>C		intron_variant
ZNF536	ENST00000706147.1	c.2323+47098G>C		intron_variant

Frequencies

GnomAD3 genomes AF: 0.0111 AC: 1694 AN: 152140 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.00348

Gnomad AMI AF: 0.0164

Gnomad AMR AF: 0.00661

Gnomad ASJ AF: 0.00231

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.00998

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.0100

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

GnomAD4 genome AF: 0.0111 AC: 1694 AN: 152258 Hom.: 15 Cov.: 32 AF XY: 0.0103 AC XY: 769 AN XY: 74452

Gnomad4 AFR AF: 0.00347

Gnomad4 AMR AF: 0.00660

Gnomad4 ASJ AF: 0.00231

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00290

Gnomad4 FIN AF: 0.00998

Gnomad4 NFE AF: 0.0189

Gnomad4 OTH AF: 0.00992

Alfa AF: 0.0172 Hom.: 5

Bravo AF: 0.0111

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.11
Dann	Benign	0.26

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10518268; hg19: chr19-31073004;