dbSNP rs1291364292: ZKSCAN7:p.Pro227Thr (chr3-44567998-C-A) – 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.679C>A(p.Pro227Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000188 in 1,439,626 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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. P227S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 27)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

ZKSCAN7
NM_001288590.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0270

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:

Genome browser will be placed here

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=0.05948189).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZKSCAN7	NM_001288590.2 link	c.679C>A	p.Pro227Thr	missense_variant	Exon 4 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.679C>A	p.Pro227Thr	missense_variant	Exon 4 of 6	2	NM_001288590.2	ENSP00000395524.1		Q9P0L1-1

Frequencies

GnomAD3 genomes

AF:

0.0000200

AC:

AN:

150024

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000390

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000234

AC:

AN:

128372

AF XY:

0.0000455

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000949

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000281

GnomAD4 exome

AF:

0.0000186

AC:

AN:

1289484

Hom.:

Cov.:

AF XY:

0.0000172

AC XY:

AN XY:

637772

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29122

American (AMR)

AF:

0.0000603

AC:

AN:

33160

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22764

East Asian (EAS)

AF:

0.0000285

AC:

AN:

35102

South Asian (SAS)

AF:

0.0000136

AC:

AN:

73732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48374

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4026

European-Non Finnish (NFE)

AF:

0.0000202

AC:

AN:

989362

Other (OTH)

AF:

0.00

AC:

AN:

53842

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000200

AC:

AN:

150142

Hom.:

Cov.:

AF XY:

0.0000273

AC XY:

AN XY:

73168

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40690

American (AMR)

AF:

0.00

AC:

AN:

15022

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3446

East Asian (EAS)

AF:

0.000390

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4644

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000148

AC:

AN:

67618

Other (OTH)

AF:

0.00

AC:

AN:

2056

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

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.29

T;.;.;T;T;.

Eigen

Benign

-0.70

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.24

M_CAP

Benign

0.015

MetaRNN

Benign

0.059

T;T;T;T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Uncertain

2.3

M;M;M;M;.;.

PhyloP100

-0.027

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.7

D;D;D;D;D;D

REVEL

Benign

0.051

Sift

Benign

0.51

T;T;T;T;D;D

Sift4G

Benign

0.57

T;T;T;T;T;D

Polyphen

0.011

B;D;D;B;.;.

Vest4

0.20

MutPred

0.27

Gain of MoRF binding (P = 0.1269);Gain of MoRF binding (P = 0.1269);Gain of MoRF binding (P = 0.1269);Gain of MoRF binding (P = 0.1269);.;.;

MVP

0.23

MPC

0.14

ClinPred

0.26

GERP RS

-0.35

Varity_R

0.080

gMVP

0.049

Mutation Taster

=85/15

polymorphism

(source)

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

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rs1291364292

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over