Variant chr7-100057866-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_145914.3(ZSCAN21):c.568G>A(p.Ala190Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,609,982 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000022 ( 1 hom. )

Consequence

ZSCAN21
NM_145914.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.177

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0113756955).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN21	NM_145914.3 linkuse as main transcript	c.568G>A	p.Ala190Thr	missense_variant	3/4	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.568G>A	p.Ala190Thr	missense_variant	3/4	1	NM_145914.3	ENSP00000292450.4	Q9Y5A6
ZSCAN21	ENST00000456748.6 linkuse as main transcript	c.568G>A	p.Ala190Thr	missense_variant	3/5	5		ENSP00000390960.2	G3V0F4
ZSCAN21	ENST00000477297.1 linkuse as main transcript	n.664G>A		non_coding_transcript_exon_variant	2/3	3
ZSCAN21	ENST00000438937.1 linkuse as main transcript	c.*25G>A		downstream_gene_variant		2		ENSP00000404207.1	C9JHD9

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00104

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000526

AC:

AN:

246988

Hom.:

AF XY:

0.0000599

AC XY:

AN XY:

133662

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:

0.000398

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000896

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000220

AC:

AN:

1457712

Hom.:

Cov.:

AF XY:

0.0000303

AC XY:

AN XY:

725192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000506

Gnomad4 SAS exome

AF:

0.000280

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152270

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000494

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 28, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.17

DANN

Benign

0.17

DEOGEN2

Benign

0.059

T;T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.00080

LIST_S2

Benign

0.48

T;T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.011

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

-1.5

N;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

0.35

N;N;.

REVEL

Benign

0.018

Sift

Benign

0.90

T;T;.

Sift4G

Benign

0.77

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.068

MutPred

0.21

Gain of glycosylation at A190 (P = 0.0137);Gain of glycosylation at A190 (P = 0.0137);.;

MVP

0.11

MPC

0.11

ClinPred

0.022

GERP RS

-0.58

Varity_R

0.031

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

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