rs2229375

Variant names:

• chr19-58067210-C-T
• rs2229375
• NM_001289401.2:c.726C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The ENST00000313434.10(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 ENST00000313434.10 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55
• Publications: 20 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.003).
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000313434.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF135	NM_001289401.2	MANE Select	c.726C>T	p.Tyr242Tyr	synonymous	Exon 5 of 5	NP_001276330.1
	ZNF135	NM_007134.1		c.798C>T	p.Tyr266Tyr	synonymous	Exon 4 of 4	NP_009065.1
	ZNF135	NM_003436.4		c.762C>T	p.Tyr254Tyr	synonymous	Exon 5 of 5	NP_003427.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF135	ENST00000313434.10	TSL:1 MANE Select	c.726C>T	p.Tyr242Tyr	synonymous	Exon 5 of 5	ENSP00000321406.5
	ZNF135	ENST00000401053.8	TSL:1	c.798C>T	p.Tyr266Tyr	synonymous	Exon 4 of 4	ENSP00000441410.1
	ZNF135	ENST00000511556.5	TSL:2	c.762C>T	p.Tyr254Tyr	synonymous	Exon 5 of 5	ENSP00000422074.1

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

GnomAD2 exomes AF: 0.400 AC: 100627 AN: 251368 AF XY: 0.401

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 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

African (AFR) AF: 0.352 AC: 11794 AN: 33480

American (AMR) AF: 0.510 AC: 22789 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 11831 AN: 26136

East Asian (EAS) AF: 0.276 AC: 10941 AN: 39700

South Asian (SAS) AF: 0.423 AC: 36493 AN: 86258

European-Finnish (FIN) AF: 0.352 AC: 18802 AN: 53414

Middle Eastern (MID) AF: 0.431 AC: 2488 AN: 5768

European-Non Finnish (NFE) AF: 0.394 AC: 438427 AN: 1112006

Other (OTH) AF: 0.396 AC: 23919 AN: 60396

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

African (AFR) AF: 0.354 AC: 14658 AN: 41422

American (AMR) AF: 0.441 AC: 6739 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.463 AC: 1606 AN: 3470

East Asian (EAS) AF: 0.227 AC: 1169 AN: 5144

South Asian (SAS) AF: 0.410 AC: 1976 AN: 4816

European-Finnish (FIN) AF: 0.352 AC: 3727 AN: 10576

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.398 AC: 27018 AN: 67960

Other (OTH) AF: 0.396 AC: 834 AN: 2108

Alfa AF: 0.405 Hom.: 24865

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.3
DANN	Benign	0.82
PhyloP100		-1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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