Genetic Variant ZSCAN21:p.Arg125Leu (chr7-100057380-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_145914.3(ZSCAN21):c.374G>T(p.Arg125Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,412,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. R125Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZSCAN21
NM_145914.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.377

Publications

0 publications found

Variant links:

Genes affected

ZSCAN21 (HGNC:13104): (zinc finger and SCAN domain containing 21) Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Predicted to be located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN21 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=0.23930702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN21	NM_145914.3 link	c.374G>T	p.Arg125Leu	missense_variant	Exon 2 of 4	ENST00000292450.9	NP_666019.1	Q9Y5A6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZSCAN21	ENST00000292450.9 link	c.374G>T	p.Arg125Leu	missense_variant	Exon 2 of 4	1	NM_145914.3	ENSP00000292450.4	Q9Y5A6
ZSCAN21	ENST00000456748.6 link	c.374G>T	p.Arg125Leu	missense_variant	Exon 2 of 5	5		ENSP00000390960.2	G3V0F4
ZSCAN21	ENST00000438937.1 link	c.374G>T	p.Arg125Leu	missense_variant	Exon 3 of 4	2		ENSP00000404207.1	C9JHD9
ZSCAN21	ENST00000477297.1 link	n.470G>T		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1412900

Hom.:

Cov.:

AF XY:

0.00000286

AC XY:

AN XY:

698508

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32160

American (AMR)

AF:

0.00

AC:

AN:

37628

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22632

East Asian (EAS)

AF:

0.00

AC:

AN:

39378

South Asian (SAS)

AF:

0.00

AC:

AN:

78308

European-Finnish (FIN)

AF:

0.0000401

AC:

AN:

49924

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5522

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1089174

Other (OTH)

AF:

0.00

AC:

AN:

58174

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

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

0.17

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.27

T;T;T

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.44

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.66

T;T;T

M_CAP

Benign

0.010

MetaRNN

Benign

0.24

T;T;T

MetaSVM

Benign

-1.2

MutationAssessor

Benign

1.7

L;.;.

PhyloP100

-0.38

PrimateAI

Benign

0.24

PROVEAN

Pathogenic

-4.6

D;D;D

REVEL

Benign

0.18

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.047

D;D;D

Polyphen

0.55

P;.;.

Vest4

0.24

MutPred

0.57

Loss of solvent accessibility (P = 0.0544);Loss of solvent accessibility (P = 0.0544);Loss of solvent accessibility (P = 0.0544);

MVP

0.46

MPC

0.25

ClinPred

0.97

GERP RS

-4.8

Varity_R

0.36

gMVP

0.23

Mutation Taster

=94/6

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

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over