Genetic Variant ZSCAN25:p.Arg191Leu (chr7-99621557-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_145115.3(ZSCAN25):c.572G>T(p.Arg191Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000756 in 1,322,322 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R191Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

ZSCAN25
NM_145115.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.339

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07739642).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN25	NM_145115.3 link	c.572G>T	p.Arg191Leu	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.572G>T	p.Arg191Leu	missense_variant	Exon 5 of 8	5	NM_145115.3	ENSP00000377708.2		Q6NSZ9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.56e-7

AC:

AN:

1322322

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

650486

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

29694

American (AMR)

AF:

0.0000301

AC:

AN:

33238

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21694

East Asian (EAS)

AF:

0.00

AC:

AN:

34464

South Asian (SAS)

AF:

0.00

AC:

AN:

66696

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4582

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1029684

Other (OTH)

AF:

0.00

AC:

AN:

53334

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.64

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.034

T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.70

.;T;T

M_CAP

Benign

0.0062

MetaRNN

Benign

0.077

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.14

N;N;.

PhyloP100

0.34

PrimateAI

Benign

0.29

PROVEAN

Benign

-2.2

N;N;.

REVEL

Benign

0.015

Sift

Benign

0.032

D;D;.

Sift4G

Benign

0.30

T;T;T

Polyphen

0.023

B;B;.

Vest4

0.31

MutPred

0.28

Gain of stability (P = 0.072);Gain of stability (P = 0.072);.;

MVP

0.072

MPC

0.34

ClinPred

0.095

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.11

gMVP

0.090

Mutation Taster

=98/2

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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7-99621557-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over