Genetic Variant ZSCAN5C:p.Ala339Thr (chr19-56208724-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001358413.3(ZSCAN5C):c.1015G>A(p.Ala339Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00434 in 1,612,294 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0043 ( 32 hom. )

Consequence

ZSCAN5C
NM_001358413.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.241

Variant links:

Genes affected

ZSCAN5C (HGNC:34294): (zinc finger and SCAN domain containing 5C) 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]

ZSCAN5C links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0059837997).

BP6

Variant 19-56208724-G-A is Benign according to our data. Variant chr19-56208724-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2650558.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN5C	NM_001358413.3 link	c.1015G>A	p.Ala339Thr	missense_variant	Exon 5 of 5	ENST00000534327.7	NP_001345342.1
ZSCAN5C	XM_047439230.1 link	c.1012G>A	p.Ala338Thr	missense_variant	Exon 4 of 4		XP_047295186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN5C	ENST00000534327.7 link	c.1015G>A	p.Ala339Thr	missense_variant	Exon 5 of 5	5	NM_001358413.3	ENSP00000435234.1		A6NGD5

Frequencies

GnomAD3 genomes

AF:

0.00425

AC:

645

AN:

151898

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000486

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00439

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00820

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00651

Gnomad OTH

AF:

0.00192

GnomAD3 exomes

AF:

0.00430

AC:

1078

AN:

250896

Hom.:

AF XY:

0.00425

AC XY:

577

AN XY:

135786

show subpopulations

Gnomad AFR exome

AF:

0.000438

Gnomad AMR exome

AF:

0.00176

Gnomad ASJ exome

AF:

0.00893

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00853

Gnomad NFE exome

AF:

0.00614

Gnomad OTH exome

AF:

0.00458

GnomAD4 exome

AF:

0.00435

AC:

6346

AN:

1460280

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

3211

AN XY:

726598

show subpopulations

Gnomad4 AFR exome

AF:

0.000539

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.00781

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00861

Gnomad4 NFE exome

AF:

0.00477

Gnomad4 OTH exome

AF:

0.00409

GnomAD4 genome

AF:

0.00424

AC:

645

AN:

152014

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

316

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000484

Gnomad4 AMR

AF:

0.00438

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00820

Gnomad4 NFE

AF:

0.00651

Gnomad4 OTH

AF:

0.00190

Alfa

AF:

0.00790

Hom.:

Bravo

AF:

0.00399

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00337

AC:

ExAC

AF:

0.00473

AC:

574

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00545

EpiControl

AF:

0.00492

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZSCAN5C: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.90

DANN

Benign

0.81

DEOGEN2

Benign

0.0018

T;T

Eigen

Benign

-0.81

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.54

.;T

M_CAP

Benign

0.00026

MetaRNN

Benign

0.0060

T;T

MetaSVM

Benign

-0.94

PROVEAN

Benign

-0.89

N;N

REVEL

Benign

0.0090

Sift

Benign

0.14

T;T

Sift4G

Benign

0.55

T;T

Vest4

0.053

MVP

0.092

MPC

0.0071

ClinPred

0.0055

GERP RS

-0.014

Varity_R

0.047

gMVP

0.11

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