Genetic Variant ZKSCAN7:p.Asp186Asn (chr3-44565619-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001288590.2(ZKSCAN7):c.556G>A(p.Asp186Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,457,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

ZKSCAN7
NM_001288590.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.179

Publications

1 publications found

Variant links:

Genes affected

ZKSCAN7 (HGNC:12955): (zinc finger with KRAB and SCAN domains 7) 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 active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZKSCAN7 links:

ZKSCAN7-AS1 (HGNC:53964): (ZKSCAN7 ZNF cluster antisense RNA 1)

ZKSCAN7-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13124254).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZKSCAN7	NM_001288590.2 link	c.556G>A	p.Asp186Asn	missense_variant	Exon 3 of 6	ENST00000426540.6	NP_001275519.1	Q9P0L1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZKSCAN7	ENST00000426540.6 link	c.556G>A	p.Asp186Asn	missense_variant	Exon 3 of 6	2	NM_001288590.2	ENSP00000395524.1		Q9P0L1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000405

AC:

AN:

246932

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000343

AC:

AN:

1457370

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724870

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33316

American (AMR)

AF:

0.00

AC:

AN:

43710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26002

East Asian (EAS)

AF:

0.00

AC:

AN:

39538

South Asian (SAS)

AF:

0.00

AC:

AN:

85146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53392

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1110254

Other (OTH)

AF:

0.00

AC:

AN:

60256

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.556G>A (p.D186N) alteration is located in exon 3 (coding exon 2) of the ZKSCAN7 gene. This alteration results from a G to A substitution at nucleotide position 556, causing the aspartic acid (D) at amino acid position 186 to be replaced by an asparagine (N). 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

0.097

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.067

T;.;.;T;T;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.14

M_CAP

Benign

0.0081

MetaRNN

Benign

0.13

T;T;T;T;T;T

MetaSVM

Benign

-1.0

PhyloP100

0.18

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.9

N;D;D;N;N;N

REVEL

Benign

0.067

Sift

Benign

0.11

T;T;T;T;T;T

Sift4G

Benign

0.52

T;T;T;T;T;D

Polyphen

0.28

B;D;D;B;.;.

Vest4

0.19

MutPred

0.15

Gain of glycosylation at P184 (P = 0.105);Gain of glycosylation at P184 (P = 0.105);Gain of glycosylation at P184 (P = 0.105);Gain of glycosylation at P184 (P = 0.105);.;.;

MVP

0.35

MPC

0.25

ClinPred

0.82

GERP RS

3.2

Varity_R

0.061

gMVP

0.10

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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chr3-44565619-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over