Variant 6-28148765-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006298.4(ZKSCAN8):c.358G>C(p.Glu120Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,878 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZKSCAN8
NM_006298.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.63

Variant links:

Genes affected

ZKSCAN8 (HGNC:12983): (zinc finger with KRAB and SCAN domains 8) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZKSCAN8 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZKSCAN8	NM_006298.4 linkuse as main transcript	c.358G>C	p.Glu120Gln	missense_variant	2/6	ENST00000330236.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZKSCAN8	ENST00000330236.7 linkuse as main transcript	c.358G>C	p.Glu120Gln	missense_variant	2/6	1	NM_006298.4	P1	Q15776-1
ZKSCAN8	ENST00000457389.6 linkuse as main transcript	c.358G>C	p.Glu120Gln	missense_variant	3/7	1		P1	Q15776-1
ZKSCAN8	ENST00000606198.5 linkuse as main transcript	c.358G>C	p.Glu120Gln	missense_variant, NMD_transcript_variant	2/6	1			Q15776-2
ZKSCAN8	ENST00000536028.2 linkuse as main transcript	c.358G>C	p.Glu120Gln	missense_variant, NMD_transcript_variant	3/7	2			Q15776-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251228

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2022

The c.358G>C (p.E120Q) alteration is located in exon 2 (coding exon 1) of the ZKSCAN8 gene. This alteration results from a G to C substitution at nucleotide position 358, causing the glutamic acid (E) at amino acid position 120 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.40

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.055

T;T

Eigen

Pathogenic

0.86

Eigen_PC

Pathogenic

0.78

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.0079

MetaRNN

Uncertain

0.68

D;D

MetaSVM

Benign

-0.96

MutationAssessor

Pathogenic

3.2

M;M

MutationTaster

Benign

0.92

D;D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.4

N;N

REVEL

Benign

0.28

Sift

Uncertain

0.0020

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

D;D

Vest4

0.41

MutPred

0.83

Loss of disorder (P = 0.109);Loss of disorder (P = 0.109);

MVP

0.74

MPC

0.99

ClinPred

0.87

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.35

gMVP

0.39

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