rs2229375

Positions:

• chr19-58067210-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001289401.2(ZNF135):​c.726C>T​(p.Tyr242Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.394 in 1,613,856 control chromosomes in the GnomAD database, including 127,026 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 0.38 (11230 hom., cov: 32)
  • Exomes 𝑓: 0.40 (115796 hom.)
• Consequence: ZNF135 NM_001289401.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP7: Synonymous conserved (PhyloP=-1.55 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF135	NM_001289401.2	c.726C>T	p.Tyr242Tyr	synonymous_variant	5/5	ENST00000313434.10	NP_001276330.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF135	ENST00000313434.10	c.726C>T	p.Tyr242Tyr	synonymous_variant	5/5	1	NM_001289401.2	ENSP00000321406.5

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58060 AN: 151856 Hom.: 11218 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.463

Gnomad EAS AF: 0.227

Gnomad SAS AF: 0.410

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.398

Gnomad OTH AF: 0.401

GnomAD3 exomes AF: 0.400 AC: 100627 AN: 251368 Hom.: 20987 AF XY: 0.401 AC XY: 54520 AN XY: 135868

Gnomad AFR exome AF: 0.347

Gnomad AMR exome AF: 0.514

Gnomad ASJ exome AF: 0.463

Gnomad EAS exome AF: 0.204

Gnomad SAS exome AF: 0.420

Gnomad FIN exome AF: 0.359

Gnomad NFE exome AF: 0.401

Gnomad OTH exome AF: 0.427

GnomAD4 exome AF: 0.395 AC: 577484 AN: 1461882 Hom.: 115796 Cov.: 87 AF XY: 0.396 AC XY: 288093 AN XY: 727244

Gnomad4 AFR exome AF: 0.352

Gnomad4 AMR exome AF: 0.510

Gnomad4 ASJ exome AF: 0.453

Gnomad4 EAS exome AF: 0.276

Gnomad4 SAS exome AF: 0.423

Gnomad4 FIN exome AF: 0.352

Gnomad4 NFE exome AF: 0.394

Gnomad4 OTH exome AF: 0.396

GnomAD4 genome AF: 0.382 AC: 58108 AN: 151974 Hom.: 11230 Cov.: 32 AF XY: 0.380 AC XY: 28197 AN XY: 74298

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.463

Gnomad4 EAS AF: 0.227

Gnomad4 SAS AF: 0.410

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.398

Gnomad4 OTH AF: 0.396

Alfa AF: 0.406 Hom.: 20731

Bravo AF: 0.387

Asia WGS AF: 0.292 AC: 1016 AN: 3478

EpiCase AF: 0.413

EpiControl AF: 0.424

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.82

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2229375; hg19: chr19-58578578; COSMIC: COSV57881039; COSMIC: COSV57881039;