Variant 7-99512571-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145102.4(ZKSCAN5):c.533C>T(p.Pro178Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,614,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

ZKSCAN5
NM_145102.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.99

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23287675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZKSCAN5	NM_145102.4 linkuse as main transcript	c.533C>T	p.Pro178Leu	missense_variant	3/7	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.533C>T	p.Pro178Leu	missense_variant	3/7	1	NM_145102.4	ENSP00000322872.5	Q9Y2L8
ZKSCAN5	ENST00000394170.6 linkuse as main transcript	c.533C>T	p.Pro178Leu	missense_variant	3/7	1		ENSP00000377725.2	Q9Y2L8
ZKSCAN5	ENST00000451158.5 linkuse as main transcript	c.533C>T	p.Pro178Leu	missense_variant	3/7	1		ENSP00000392104.1	Q9Y2L8
ZKSCAN5	ENST00000454175.1 linkuse as main transcript	n.533C>T		non_coding_transcript_exon_variant	2/5	1		ENSP00000405716.1	F8WBD4

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152220

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:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251044

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135718

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 SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000353

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000116

AC:

AN:

1461796

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

727208

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:

0.0000696

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74358

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000330

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

Oct 05, 2023

The c.533C>T (p.P178L) alteration is located in exon 3 (coding exon 2) of the ZKSCAN5 gene. This alteration results from a C to T substitution at nucleotide position 533, causing the proline (P) at amino acid position 178 to be replaced by a leucine (L). 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

0.13

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.054

T;T;T

Eigen

Uncertain

0.21

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.63

LIST_S2

Uncertain

0.86

.;.;D

M_CAP

Benign

0.0044

MetaRNN

Benign

0.23

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Uncertain

2.1

M;M;M

PrimateAI

Benign

0.37

PROVEAN

Benign

-2.0

N;N;N

REVEL

Benign

0.16

Sift

Uncertain

0.012

D;D;D

Sift4G

Uncertain

0.025

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.45

MutPred

0.26

Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);Loss of loop (P = 0.0603);

MVP

0.39

MPC

0.26

ClinPred

0.48

GERP RS

4.8

Varity_R

0.11

gMVP

0.38

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

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