Variant 19-58066946-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001289401.2(ZNF135):c.462G>A(p.Thr154Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00318 in 1,614,164 control chromosomes in the GnomAD database, including 119 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 61 hom., cov: 33)

Exomes 𝑓: 0.0019 ( 58 hom. )

Consequence

ZNF135
NM_001289401.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.88

Variant links:

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]

ZNF135 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 19-58066946-G-A is Benign according to our data. Variant chr19-58066946-G-A is described in ClinVar as [Benign]. Clinvar id is 781538.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.88 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0501 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZNF135	NM_001289401.2 linkuse as main transcript	c.462G>A	p.Thr154Thr	synonymous_variant	5/5	ENST00000313434.10	NP_001276330.1	P52742-1Q8N9M3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZNF135	ENST00000313434.10 linkuse as main transcript	c.462G>A	p.Thr154Thr	synonymous_variant	5/5	1	NM_001289401.2	ENSP00000321406.5		P52742-1

Frequencies

GnomAD3 genomes

AF:

0.0152

AC:

2307

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0520

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00471

Gnomad ASJ

AF:

0.0110

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.00457

AC:

1147

AN:

251254

Hom.:

AF XY:

0.00358

AC XY:

486

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.0523

Gnomad AMR exome

AF:

0.00350

Gnomad ASJ exome

AF:

0.0103

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000475

Gnomad OTH exome

AF:

0.00245

GnomAD4 exome

AF:

0.00194

AC:

2830

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00171

AC XY:

1243

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.0535

Gnomad4 AMR exome

AF:

0.00376

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000316

Gnomad4 OTH exome

AF:

0.00351

GnomAD4 genome

AF:

0.0152

AC:

2309

AN:

152294

Hom.:

Cov.:

AF XY:

0.0145

AC XY:

1077

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0519

Gnomad4 AMR

AF:

0.00471

Gnomad4 ASJ

AF:

0.0110

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00380

Hom.:

Bravo

AF:

0.0171

Asia WGS

AF:

0.00289

AC:

AN:

3478

EpiCase

AF:

0.000545

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 04, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

2.0

DANN

Benign

0.54

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over