Variant chr6-28153353-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000330236.7(ZKSCAN8):c.1073C>A(p.Ala358Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZKSCAN8
ENST00000330236.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0290

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34710383).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN8	NM_006298.4 linkuse as main transcript	c.1073C>A	p.Ala358Asp	missense_variant	6/6	ENST00000330236.7	NP_006289.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZKSCAN8	ENST00000330236.7 linkuse as main transcript	c.1073C>A	p.Ala358Asp	missense_variant	6/6	1	NM_006298.4	ENSP00000332750	P1	Q15776-1
ZKSCAN8	ENST00000457389.6 linkuse as main transcript	c.1073C>A	p.Ala358Asp	missense_variant	7/7	1		ENSP00000402948	P1	Q15776-1
ZKSCAN8	ENST00000606198.5 linkuse as main transcript	c.*610C>A		3_prime_UTR_variant, NMD_transcript_variant	6/6	1		ENSP00000475589		Q15776-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 20, 2023

The c.1073C>A (p.A358D) alteration is located in exon 6 (coding exon 5) of the ZKSCAN8 gene. This alteration results from a C to A substitution at nucleotide position 1073, causing the alanine (A) at amino acid position 358 to be replaced by an aspartic acid (D). 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

Pathogenic

0.75

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.084

T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.20

.;T

M_CAP

Benign

0.0092

MetaRNN

Benign

0.35

T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

0.66

D;D

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.0

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

1.0

D;D

Vest4

0.53

MutPred

0.66

Loss of catalytic residue at A358 (P = 0.0213);Loss of catalytic residue at A358 (P = 0.0213);

MVP

0.55

MPC

1.2

ClinPred

0.97

GERP RS

5.1

Varity_R

0.48

gMVP

0.24

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over