Variant 1-33479694-G-T 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_001377376.1(ZSCAN20):c.406G>T(p.Ala136Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ZSCAN20
NM_001377376.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.585

Variant links:

Genes affected

ZSCAN20 (HGNC:13093): (zinc finger and SCAN domain containing 20) 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]

ZSCAN20 links:

ZSCAN20 (HGNC:):

ZSCAN20 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=0.051526815).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZSCAN20	NM_001377376.1 linkuse as main transcript	c.406G>T	p.Ala136Ser	missense_variant	2/8	ENST00000684572.1	NP_001364305.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZSCAN20	ENST00000684572.1 linkuse as main transcript	c.406G>T	p.Ala136Ser	missense_variant	2/8		NM_001377376.1	ENSP00000507139.1	P17040-1
ZSCAN20	ENST00000373413.2 linkuse as main transcript	c.406G>T	p.Ala136Ser	missense_variant	2/4	1		ENSP00000362512.1	P17040-4
ZSCAN20	ENST00000361328.7 linkuse as main transcript	c.406G>T	p.Ala136Ser	missense_variant	2/8	2		ENSP00000355053.3	P17040-1
ZSCAN20	ENST00000480917.1 linkuse as main transcript	n.548G>T		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1398950

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

691390

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 10, 2021

The c.406G>T (p.A136S) alteration is located in exon 2 (coding exon 1) of the ZSCAN20 gene. This alteration results from a G to T substitution at nucleotide position 406, causing the alanine (A) at amino acid position 136 to be replaced by a serine (S). 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

0.12

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.66

CADD

Benign

0.95

DANN

Benign

0.66

DEOGEN2

Benign

0.048

T;.

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.13

T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

0.89

L;L

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.54

N;N

REVEL

Benign

0.024

Sift

Benign

0.096

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.12

B;B

Vest4

0.12

MutPred

0.41

Gain of glycosylation at A136 (P = 0.0073);Gain of glycosylation at A136 (P = 0.0073);

MVP

0.11

MPC

0.20

ClinPred

0.081

GERP RS

3.0

Varity_R

0.036

gMVP

0.12

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over