Variant 6-28365902-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024493.4(ZKSCAN3):c.1234A>G(p.Ser412Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,461,008 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

ZKSCAN3
NM_024493.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.31

Variant links:

Genes affected

ZKSCAN3 (HGNC:13853): (zinc finger with KRAB and SCAN domains 3) Enables DNA-binding transcription repressor activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and chromatin binding activity. Involved in several processes, including negative regulation of autophagy; negative regulation of cellular senescence; and regulation of transcription, DNA-templated. Located in cytoplasm and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ZKSCAN3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11505887).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN3	NM_024493.4 link	c.1234A>G	p.Ser412Gly	missense_variant	6/6	ENST00000252211.7	NP_077819.2	Q9BRR0-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZKSCAN3	ENST00000252211.7 link	c.1234A>G	p.Ser412Gly	missense_variant	6/6	1	NM_024493.4	ENSP00000252211.2	Q9BRR0-1
ZKSCAN3	ENST00000377255.3 link	c.1234A>G	p.Ser412Gly	missense_variant	7/7	1		ENSP00000366465.1	Q9BRR0-1
ZKSCAN3	ENST00000341464.9 link	c.790A>G	p.Ser264Gly	missense_variant	5/5	2		ENSP00000341883.5	Q9BRR0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461008

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

726776

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:

0.0000171

Gnomad4 OTH exome

AF:

0.0000166

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

Nov 14, 2023

The c.1234A>G (p.S412G) alteration is located in exon 7 (coding exon 5) of the ZKSCAN3 gene. This alteration results from a A to G substitution at nucleotide position 1234, causing the serine (S) at amino acid position 412 to be replaced by a glycine (G). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.012

T;.;T

Eigen

Benign

-0.063

Eigen_PC

Benign

-0.15

FATHMM_MKL

Benign

0.27

LIST_S2

Benign

0.50

T;T;.

M_CAP

Benign

0.0072

MetaRNN

Benign

0.12

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;.;L

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.060

Sift

Benign

0.35

T;T;T

Sift4G

Benign

0.50

T;T;T

Polyphen

1.0

D;.;D

Vest4

0.076

MutPred

0.35

Loss of stability (P = 0.084);.;Loss of stability (P = 0.084);

MVP

0.26

MPC

0.61

ClinPred

0.43

GERP RS

2.8

Varity_R

0.061

gMVP

0.030

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