Variant 7-99506457-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_145102.4(ZKSCAN5):c.413A>G(p.Gln138Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000074 in 1,607,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000058 ( 0 hom. )

Consequence

ZKSCAN5
NM_145102.4 missense, splice_region

Scores

Splicing: ADA: 0.9937

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.84

Variant links:

Genes affected

ZKSCAN5 (HGNC:12867): (zinc finger with KRAB and SCAN domains 5) This gene encodes a zinc finger protein of the Kruppel family. The protein contains a SCAN box and a KRAB A domain and may be involved in transcriptional regulation. A similar protein in mouse is differentially expressed in spermatogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]

ZKSCAN5 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN5	NM_145102.4 linkuse as main transcript	c.413A>G	p.Gln138Arg	missense_variant, splice_region_variant	2/7	ENST00000326775.10	NP_659570.1	Q9Y2L8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZKSCAN5	ENST00000326775.10 linkuse as main transcript	c.413A>G	p.Gln138Arg	missense_variant, splice_region_variant	2/7	1	NM_145102.4	ENSP00000322872.5	Q9Y2L8
ZKSCAN5	ENST00000394170.6 linkuse as main transcript	c.413A>G	p.Gln138Arg	missense_variant, splice_region_variant	2/7	1		ENSP00000377725.2	Q9Y2L8
ZKSCAN5	ENST00000451158.5 linkuse as main transcript	c.413A>G	p.Gln138Arg	missense_variant, splice_region_variant	2/7	1		ENSP00000392104.1	Q9Y2L8
ZKSCAN5	ENST00000454175.1 linkuse as main transcript	n.413A>G		splice_region_variant, non_coding_transcript_exon_variant	1/5	1		ENSP00000405716.1	F8WBD4

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000110

AC:

AN:

245954

Hom.:

AF XY:

0.0000601

AC XY:

AN XY:

133054

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.0000882

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000271

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000577

AC:

AN:

1454828

Hom.:

Cov.:

AF XY:

0.0000567

AC XY:

AN XY:

722944

show subpopulations

Gnomad4 AFR exome

AF:

0.00120

Gnomad4 AMR exome

AF:

0.000158

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:

0.0000199

Gnomad4 OTH exome

AF:

0.000183

GnomAD4 genome

AF:

0.000230

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.000174

AC XY:

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000634

Hom.:

Bravo

AF:

0.000321

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000124

AC:

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

Jul 05, 2022

The c.413A>G (p.Q138R) alteration is located in exon 2 (coding exon 1) of the ZKSCAN5 gene. This alteration results from a A to G substitution at nucleotide position 413, causing the glutamine (Q) at amino acid position 138 to be replaced by an arginine (R). 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

0.15

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

T;T;T

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.74

.;.;T

M_CAP

Benign

0.0068

MetaRNN

Benign

0.060

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

L;L;L

PrimateAI

Benign

0.48

PROVEAN

Benign

-1.3

N;N;N

REVEL

Benign

0.18

Sift

Benign

0.061

T;T;T

Sift4G

Benign

0.38

T;T;T

Polyphen

0.99

D;D;D

Vest4

0.24

MVP

0.47

MPC

0.72

ClinPred

0.047

GERP RS

4.7

Varity_R

0.13

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.99

dbscSNV1_RF

Pathogenic

0.93

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over