Genetic Variant ZKSCAN7:p.Ser15Thr (chr3-44557091-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001288590.2(ZKSCAN7):c.44G>C(p.Ser15Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S15N) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

ZKSCAN7
NM_001288590.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0390

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.029322416).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZKSCAN7	NM_001288590.2 link	c.44G>C	p.Ser15Thr	missense_variant	Exon 2 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.44G>C	p.Ser15Thr	missense_variant	Exon 2 of 6	2	NM_001288590.2	ENSP00000395524.1		Q9P0L1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251418

AF XY:

0.00000736

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1461888

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.082

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

5.6

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.044

T;.;.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.025

M_CAP

Benign

0.0017

MetaRNN

Benign

0.029

T;T;T;T

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.59

N;N;N;N

PhyloP100

-0.039

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.46

N;N;N;N

REVEL

Benign

0.058

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.98

T;T;T;T

Polyphen

0.0

B;B;B;B

Vest4

0.16

MutPred

0.19

Gain of catalytic residue at F18 (P = 0.1067);Gain of catalytic residue at F18 (P = 0.1067);Gain of catalytic residue at F18 (P = 0.1067);Gain of catalytic residue at F18 (P = 0.1067);

MVP

0.092

MPC

0.061

ClinPred

0.045

GERP RS

-1.6

Varity_R

0.046

gMVP

0.16

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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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3-44557091-G-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over