rs1549492

Positions:

• chr19-58073880-A-G

Variant summary

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

The ENST00000515535.1(ZNF135):​c.161-7813A>G variant causes a intron, NMD transcript change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.691 in 151,970 control chromosomes in the GnomAD database, including 36,574 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 0.69 (36574 hom., cov: 31)
• Consequence: ZNF135 ENST00000515535.1 intron, NMD_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.632

Genes affected

ZNF135 (HGNC:12919): (zinc finger protein 135) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZNF135	ENST00000515535.1	c.161-7813A>G		intron_variant, NMD_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.691 AC: 104976 AN: 151852 Hom.: 36541 Cov.: 31

Gnomad AFR AF: 0.761

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.674

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.702

Gnomad MID AF: 0.684

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.693

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

GnomAD4 genome AF: 0.691 AC: 105060 AN: 151970 Hom.: 36574 Cov.: 31 AF XY: 0.688 AC XY: 51064 AN XY: 74258

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.675

Gnomad4 ASJ AF: 0.697

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.666

Gnomad4 FIN AF: 0.702

Gnomad4 NFE AF: 0.668

Gnomad4 OTH AF: 0.687

Alfa AF: 0.679 Hom.: 4393

Bravo AF: 0.695

Asia WGS AF: 0.545 AC: 1900 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	7.1
DANN	Benign	0.71

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1549492; hg19: chr19-58585248;