Variant chr7-100023837-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_003439.4(ZKSCAN1):c.331G>A(p.Glu111Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

ZKSCAN1
NM_003439.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.83

Variant links:

Genes affected

ZKSCAN1 (HGNC:13101): (zinc finger with KRAB and SCAN domains 1) This gene encodes a member of the Kruppel C2H2-type zinc-finger family of proteins. This encoded protein may function as a transcription factor that regulates the expression of GABA type-A receptors in the brain. Transcripts from this gene have been shown to form stable and abundant circular RNAs. Elevated expression of this gene has been observed in gastric cancer and the encoded protein may stimulate migration and invasion of human gastric cancer cells. [provided by RefSeq, Oct 2016]

ZKSCAN1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.799

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZKSCAN1	NM_003439.4 linkuse as main transcript	c.331G>A	p.Glu111Lys	missense_variant	2/6	ENST00000324306.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZKSCAN1	ENST00000324306.11 linkuse as main transcript	c.331G>A	p.Glu111Lys	missense_variant	2/6	1	NM_003439.4	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461842

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727232

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

Feb 15, 2023

The c.331G>A (p.E111K) alteration is located in exon 2 (coding exon 1) of the ZKSCAN1 gene. This alteration results from a G to A substitution at nucleotide position 331, causing the glutamic acid (E) at amino acid position 111 to be replaced by a lysine (K). 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

0.47

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;.;T;.

Eigen

Benign

0.019

Eigen_PC

Benign

0.096

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.85

D;.;D;T

M_CAP

Benign

0.012

MetaRNN

Pathogenic

0.80

D;D;D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

M;.;.;.

MutationTaster

Benign

0.80

D;D;D

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-3.0

D;D;D;.

REVEL

Benign

0.17

Sift

Uncertain

0.0030

D;D;D;.

Sift4G

Uncertain

0.0070

D;D;D;D

Polyphen

0.076

B;B;.;B

Vest4

0.61

MutPred

0.85

Gain of methylation at E111 (P = 0.0163);.;Gain of methylation at E111 (P = 0.0163);.;

MVP

0.50

MPC

0.70

ClinPred

0.96

GERP RS

3.7

Varity_R

0.39

gMVP

0.63

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