Variant 6-28251599-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The ENST00000377294.3(ZKSCAN4):c.382T>C(p.Leu128=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,614,094 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0026 ( 15 hom. )

Consequence

ZKSCAN4
ENST00000377294.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.16

Variant links:

Genes affected

ZKSCAN4 (HGNC:13854): (zinc finger with KRAB and SCAN domains 4) Enables identical protein binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZKSCAN4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 6-28251599-A-G is Benign according to our data. Variant chr6-28251599-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2656318.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.16 with no splicing effect.

BS1

Variant frequency is greater than expected in population mid. gnomad4_exome allele frequency = 0.00264 (3855/1461886) while in subpopulation MID AF= 0.0276 (159/5766). AF 95% confidence interval is 0.0241. There are 15 homozygotes in gnomad4_exome. There are 2130 alleles in male gnomad4_exome subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN4	NM_019110.5 linkuse as main transcript	c.382T>C	p.Leu128=	synonymous_variant	1/5	ENST00000377294.3	NP_061983.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZKSCAN4	ENST00000377294.3 linkuse as main transcript	c.382T>C	p.Leu128=	synonymous_variant	1/5	1	NM_019110.5	ENSP00000366509	P1

Frequencies

GnomAD3 genomes

AF:

0.00220

AC:

335

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00419

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00116

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00246

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00358

AC:

898

AN:

250626

Hom.:

AF XY:

0.00421

AC XY:

571

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.000253

Gnomad AMR exome

AF:

0.00359

Gnomad ASJ exome

AF:

0.0120

Gnomad EAS exome

AF:

0.000761

Gnomad SAS exome

AF:

0.00627

Gnomad FIN exome

AF:

0.000739

Gnomad NFE exome

AF:

0.00345

Gnomad OTH exome

AF:

0.00590

GnomAD4 exome

AF:

0.00264

AC:

3855

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

2130

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000418

Gnomad4 AMR exome

AF:

0.00322

Gnomad4 ASJ exome

AF:

0.0121

Gnomad4 EAS exome

AF:

0.00101

Gnomad4 SAS exome

AF:

0.00712

Gnomad4 FIN exome

AF:

0.000936

Gnomad4 NFE exome

AF:

0.00201

Gnomad4 OTH exome

AF:

0.00472

GnomAD4 genome

AF:

0.00220

AC:

335

AN:

152208

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.000433

Gnomad4 AMR

AF:

0.00418

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.00116

Gnomad4 SAS

AF:

0.00436

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.00246

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00456

Hom.:

Bravo

AF:

0.00236

EpiCase

AF:

0.00333

EpiControl

AF:

0.00492

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

May 01, 2022

ZKSCAN4: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.6

DANN

Benign

0.65

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