Variant chr7-100057379-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_145914.3(ZSCAN21):c.373C>T(p.Arg125Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000364 in 1,565,304 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

ZSCAN21
NM_145914.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.954

Variant links:

Genes affected

ZSCAN21 (HGNC:13104): (zinc finger and SCAN domain containing 21) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN21 links:

ZSCAN21 (HGNC:):

ZSCAN21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28696328).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN21	NM_145914.3 linkuse as main transcript	c.373C>T	p.Arg125Trp	missense_variant	2/4	ENST00000292450.9	NP_666019.1	Q9Y5A6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZSCAN21	ENST00000292450.9 linkuse as main transcript	c.373C>T	p.Arg125Trp	missense_variant	2/4	1	NM_145914.3	ENSP00000292450.4	Q9Y5A6
ZSCAN21	ENST00000456748.6 linkuse as main transcript	c.373C>T	p.Arg125Trp	missense_variant	2/5	5		ENSP00000390960.2	G3V0F4
ZSCAN21	ENST00000438937.1 linkuse as main transcript	c.373C>T	p.Arg125Trp	missense_variant	3/4	2		ENSP00000404207.1	C9JHD9
ZSCAN21	ENST00000477297.1 linkuse as main transcript	n.469C>T		non_coding_transcript_exon_variant	1/3	3

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000346

AC:

AN:

202072

Hom.:

AF XY:

0.0000369

AC XY:

AN XY:

108514

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000110

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000115

Gnomad SAS exome

AF:

0.0000468

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000361

AC:

AN:

1413000

Hom.:

Cov.:

AF XY:

0.0000458

AC XY:

AN XY:

698546

show subpopulations

Gnomad4 AFR exome

AF:

0.0000311

Gnomad4 AMR exome

AF:

0.0000797

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000102

Gnomad4 SAS exome

AF:

0.0000511

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000358

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152304

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000529

ExAC

AF:

0.00000825

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Apr 01, 2024

The c.373C>T (p.R125W) alteration is located in exon 2 (coding exon 1) of the ZSCAN21 gene. This alteration results from a C to T substitution at nucleotide position 373, causing the arginine (R) at amino acid position 125 to be replaced by a tryptophan (W). 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

0.19

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.43

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.28

T;T;T

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.73

T;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.29

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Pathogenic

3.1

M;.;.

PrimateAI

Benign

0.26

PROVEAN

Pathogenic

-5.6

D;D;D

REVEL

Benign

0.17

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0010

D;D;D

Polyphen

0.99

D;.;.

Vest4

0.27

MVP

0.76

MPC

0.49

ClinPred

0.64

GERP RS

2.8

Varity_R

0.41

gMVP

0.27

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