Genetic Variant ZSCAN32:p.Ala636Val (chr16-3383039-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001284527.2(ZSCAN32):c.1907C>T(p.Ala636Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,614,008 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

ZSCAN32
NM_001284527.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.63

Variant links:

Genes affected

ZSCAN32 (HGNC:20812): (zinc finger and SCAN domain containing 32) Enables identical protein 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]

ZSCAN32 links:

ENSG00000285329 (HGNC:):

ENSG00000285329 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=0.025046706).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN32	NM_001284527.2 link	c.1907C>T	p.Ala636Val	missense_variant	Exon 7 of 7	ENST00000396852.9	NP_001271456.1	Q9NX65-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN32	ENST00000396852.9 link	c.1907C>T	p.Ala636Val	missense_variant	Exon 7 of 7	1	NM_001284527.2	ENSP00000380061.4		Q9NX65-1
ENSG00000285329	ENST00000575785.2 link	n.-13+17857G>A		intron_variant	Intron 1 of 4	4		ENSP00000477472.1		V9GZ69

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251232

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135758

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000821

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727210

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

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:

0.00000360

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000945

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 26, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1271C>T (p.A424V) alteration is located in exon 6 (coding exon 3) of the ZSCAN32 gene. This alteration results from a C to T substitution at nucleotide position 1271, causing the alanine (A) at amino acid position 424 to be replaced by a valine (V). 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

0.21

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.048

DANN

Benign

0.68

DEOGEN2

Benign

0.016

T;.;.;T;.

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.000050

LIST_S2

Benign

0.65

T;T;T;.;.

M_CAP

Benign

0.00090

MetaRNN

Benign

0.025

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.44

N;.;.;N;.

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.4

N;.;N;N;N

REVEL

Benign

0.014

Sift

Benign

0.40

T;.;T;T;T

Sift4G

Benign

0.29

T;T;T;T;T

Vest4

0.099

MVP

0.092

MPC

0.016

ClinPred

0.060

GERP RS

-7.4

Varity_R

0.010

gMVP

0.013

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