Genetic Variant NM_145115.3:c.503G>C (chr7-99621488-G-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_145115.3(ZSCAN25):c.503G>C(p.Gly168Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000036 in 1,582,054 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

ZSCAN25
NM_145115.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.68

Publications

1 publications found

Variant links:

Genes affected

ZSCAN25 (HGNC:21961): (zinc finger and SCAN domain containing 25) This gene encodes a protein that bears some similarity to zinc finger proteins, which are involved in DNA binding and protein-protein interactions. Multiple alternatively spliced transcript variants have been identified, but the full-length nature for most of them has not been determined. [provided by RefSeq, Jul 2008]

ZSCAN25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.055244684).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN25	NM_145115.3 link	c.503G>C	p.Gly168Ala	missense_variant	Exon 5 of 8	ENST00000394152.7	NP_660090.2	Q6NSZ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZSCAN25	ENST00000394152.7 link	c.503G>C	p.Gly168Ala	missense_variant	Exon 5 of 8	5	NM_145115.3	ENSP00000377708.2		Q6NSZ9-1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152250

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000252

AC:

AN:

238442

AF XY:

0.0000232

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000274

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000364

AC:

AN:

1429804

Hom.:

Cov.:

AF XY:

0.0000394

AC XY:

AN XY:

710214

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32682

American (AMR)

AF:

0.00

AC:

AN:

42494

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25220

East Asian (EAS)

AF:

0.0000263

AC:

AN:

38042

South Asian (SAS)

AF:

0.000219

AC:

AN:

82372

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52704

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5604

European-Non Finnish (NFE)

AF:

0.0000256

AC:

AN:

1091972

Other (OTH)

AF:

0.0000852

AC:

AN:

58714

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152250

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41472

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5198

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68050

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.0000189

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 30, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.503G>C (p.G168A) alteration is located in exon 5 (coding exon 2) of the ZSCAN25 gene. This alteration results from a G to C substitution at nucleotide position 503, causing the glycine (G) at amino acid position 168 to be replaced by an alanine (A). 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

0.15

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.68

CADD

Benign

(source)

DANN

Benign

0.42

DEOGEN2

Benign

0.0097

T;T;T

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.45

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.71

.;T;T

M_CAP

Benign

0.0049

MetaRNN

Benign

0.055

T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.37

N;N;.

PhyloP100

1.7

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.37

N;N;.

REVEL

Benign

0.034

Sift

Benign

0.27

T;T;.

Sift4G

Benign

0.34

T;T;T

Polyphen

0.018

B;B;.

Vest4

0.16

MutPred

0.23

Loss of loop (P = 0.3664);Loss of loop (P = 0.3664);.;

MVP

0.081

MPC

0.38

ClinPred

0.023

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.039

gMVP

0.12

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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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NM_145115.3:c.503G>C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over