Genetic Variant NM_001358413.3:c.1015G>A (chr19-56208724-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/19 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

Publications

2 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 2650558.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001358413.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN5C	NM_001358413.3	MANE Select	c.1015G>A	p.Ala339Thr	missense	Exon 5 of 5	NP_001345342.1	A6NGD5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZSCAN5C	ENST00000534327.7	TSL:5 MANE Select	c.1015G>A	p.Ala339Thr	missense	Exon 5 of 5	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

GnomAD2 exomes

AF:

0.00430

AC:

1078

AN:

250896

AF XY:

0.00425

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 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

African (AFR)

AF:

0.000539

AC:

AN:

33396

American (AMR)

AF:

0.00224

AC:

100

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00781

AC:

204

AN:

26124

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.000209

AC:

AN:

86224

European-Finnish (FIN)

AF:

0.00861

AC:

459

AN:

53316

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00477

AC:

5299

AN:

1110690

Other (OTH)

AF:

0.00409

AC:

247

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

345

690

1036

1381

1726

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

152

304

456

608

760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00424

AC:

645

AN:

152014

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

316

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.000484

AC:

AN:

41288

American (AMR)

AF:

0.00438

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00663

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00820

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00651

AC:

443

AN:

68030

Other (OTH)

AF:

0.00190

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

125

156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00572

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

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.90

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.0018

Eigen

Benign

-0.81

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.54

M_CAP

Benign

0.00026

MetaRNN

Benign

0.0060

MetaSVM

Benign

-0.94

PhyloP100

0.24

PROVEAN

Benign

-0.89

REVEL

Benign

0.0090

Sift

Benign

0.14

Sift4G

Benign

0.55

Vest4

0.053

MVP

0.092

MPC

0.0071

ClinPred

0.0055

GERP RS

-0.014

Varity_R

0.047

gMVP

0.11

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over