Variant 6-28326778-A-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_030899.5(ZSCAN31):c.609T>G(p.Asp203Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,613,780 control chromosomes in the GnomAD database, including 2 homozygotes. 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: 𝑓 0.00017 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 2 hom. )

Consequence

ZSCAN31
NM_030899.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.63

Variant links:

Genes affected

ZSCAN31 (HGNC:14097): (zinc finger and SCAN domain containing 31) This gene encodes a protein containing multiple C2H2-type zinc finger motifs. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

ZSCAN31 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=0.012262613).

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSCAN31	NM_030899.5 linkuse as main transcript	c.609T>G	p.Asp203Glu	missense_variant	4/4	ENST00000344279.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSCAN31	ENST00000344279.11 linkuse as main transcript	c.609T>G	p.Asp203Glu	missense_variant	4/4	1	NM_030899.5	P1	Q96LW9-1

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152184

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000769

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000244

AC:

AN:

250312

Hom.:

AF XY:

0.000310

AC XY:

AN XY:

135400

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.00154

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000156

AC:

228

AN:

1461478

Hom.:

Cov.:

AF XY:

0.000191

AC XY:

139

AN XY:

727088

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000252

Gnomad4 SAS exome

AF:

0.00184

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000719

Gnomad4 OTH exome

AF:

0.000762

GnomAD4 genome

AF:

0.000171

AC:

AN:

152302

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000771

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000448

Hom.:

Bravo

AF:

0.000117

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000280

AC:

Asia WGS

AF:

0.00722

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

May 13, 2024

The c.609T>G (p.D203E) alteration is located in exon 4 (coding exon 3) of the ZSCAN31 gene. This alteration results from a T to G substitution at nucleotide position 609, causing the aspartic acid (D) at amino acid position 203 to be replaced by a glutamic acid (E). 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

-0.58

BayesDel_noAF

Benign

-0.64

CADD

Benign

0.027

DANN

Benign

0.14

DEOGEN2

Benign

0.0018

T;T;.;T;.;T;T;T;.;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.063

.;.;T;.;.;T;T;T;T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.012

T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.46

N;N;.;N;.;N;.;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.15

N;N;.;N;N;N;N;N;N;N

REVEL

Benign

0.031

Sift

Benign

1.0

T;T;.;T;T;T;T;T;T;D

Sift4G

Benign

1.0

T;T;T;T;T;T;T;.;T;T

Polyphen

0.14

B;B;.;B;.;B;.;.;.;.

Vest4

0.033

MutPred

0.18

Gain of methylation at K205 (P = 0.0943);Gain of methylation at K205 (P = 0.0943);.;Gain of methylation at K205 (P = 0.0943);.;Gain of methylation at K205 (P = 0.0943);.;.;Gain of methylation at K205 (P = 0.0943);.;

MVP

0.040

MPC

0.086

ClinPred

0.014

GERP RS

-2.7

Varity_R

0.020

gMVP

0.017

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