Variant 18-35263988-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000333206.10(ZSCAN30):c.365T>C(p.Met122Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00208 in 1,614,222 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0022 ( 12 hom. )

Consequence

ZSCAN30
ENST00000333206.10 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

Variant links:

Genes affected

ZSCAN30 (HGNC:33517): (zinc finger and SCAN domain containing 30) 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 located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN30 links:

ZNF397 (HGNC:):

ZNF397 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029987395).

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN30	NM_001112734.4 linkuse as main transcript	c.365T>C	p.Met122Thr	missense_variant	2/4	ENST00000333206.10	NP_001106205.1	Q86W11-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZSCAN30	ENST00000333206.10 linkuse as main transcript	c.365T>C	p.Met122Thr	missense_variant	2/4	1	NM_001112734.4	ENSP00000329738.4		Q86W11-1

Frequencies

GnomAD3 genomes

AF:

0.00139

AC:

211

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000531

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00179

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00188

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00116

AC:

289

AN:

249880

Hom.:

AF XY:

0.00126

AC XY:

171

AN XY:

135724

show subpopulations

Gnomad AFR exome

AF:

0.000258

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00149

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000229

Gnomad FIN exome

AF:

0.00130

Gnomad NFE exome

AF:

0.00169

Gnomad OTH exome

AF:

0.00148

GnomAD4 exome

AF:

0.00216

AC:

3153

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

1459

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00136

Gnomad4 ASJ exome

AF:

0.00111

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000301

Gnomad4 FIN exome

AF:

0.00120

Gnomad4 NFE exome

AF:

0.00257

Gnomad4 OTH exome

AF:

0.00136

GnomAD4 genome

AF:

0.00139

AC:

212

AN:

152330

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00179

Gnomad4 NFE

AF:

0.00188

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00194

Hom.:

Bravo

AF:

0.00141

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00337

AC:

ESP6500AA

AF:

0.000638

AC:

ESP6500EA

AF:

0.00154

AC:

ExAC

AF:

0.00101

AC:

122

Asia WGS

AF:

0.000577

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

Aug 30, 2022

The c.365T>C (p.M122T) alteration is located in exon 3 (coding exon 1) of the ZSCAN30 gene. This alteration results from a T to C substitution at nucleotide position 365, causing the methionine (M) at amino acid position 122 to be replaced by a threonine (T). 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

Uncertain

0.40

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

T;T;.;T;T;.

Eigen

Benign

0.13

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.62

.;T;D;T;D;T

M_CAP

Benign

0.0087

MetaRNN

Benign

0.030

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.2

M;M;.;.;.;.

MutationTaster

Benign

0.90

N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-2.3

N;N;.;.;.;.

REVEL

Benign

0.13

Sift

Uncertain

0.0030

D;D;.;.;.;.

Sift4G

Uncertain

0.029

D;D;.;D;D;D

Polyphen

0.22

B;B;.;B;.;.

Vest4

0.26

MVP

0.40

MPC

0.047

ClinPred

0.058

GERP RS

4.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.33

gMVP

0.40

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