dbSNP rs1303461267: ZSCAN21:p.Glu121Lys (chr7-100057367-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_145914.3(ZSCAN21):c.361G>A(p.Glu121Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000698 in 1,575,136 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000070 ( 0 hom. )

Consequence

ZSCAN21
NM_145914.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN21	NM_145914.3 link	c.361G>A	p.Glu121Lys	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.361G>A	p.Glu121Lys	missense_variant	Exon 2 of 4	1	NM_145914.3	ENSP00000292450.4	Q9Y5A6
ZSCAN21	ENST00000456748.6 link	c.361G>A	p.Glu121Lys	missense_variant	Exon 2 of 5	5		ENSP00000390960.2	G3V0F4
ZSCAN21	ENST00000438937.1 link	c.361G>A	p.Glu121Lys	missense_variant	Exon 3 of 4	2		ENSP00000404207.1	C9JHD9
ZSCAN21	ENST00000477297.1 link	n.457G>A		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000703

AC:

AN:

1422928

Hom.:

Cov.:

AF XY:

0.00000568

AC XY:

AN XY:

704682

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32340

American (AMR)

AF:

0.00

AC:

AN:

38800

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23280

East Asian (EAS)

AF:

0.00

AC:

AN:

39448

South Asian (SAS)

AF:

0.0000249

AC:

AN:

80206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50772

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5570

European-Non Finnish (NFE)

AF:

0.00000457

AC:

AN:

1093868

Other (OTH)

AF:

0.0000512

AC:

AN:

58644

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68036

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 01, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.361G>A (p.E121K) alteration is located in exon 2 (coding exon 1) of the ZSCAN21 gene. This alteration results from a G to A substitution at nucleotide position 361, causing the glutamic acid (E) at amino acid position 121 to be replaced by a lysine (K). 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

Pathogenic

0.59

BayesDel_addAF

Uncertain

0.064

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.35

T;T;T

Eigen

Pathogenic

0.78

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

D;D;D

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.55

D;D;D

MetaSVM

Benign

-0.67

MutationAssessor

Pathogenic

3.5

H;.;.

PhyloP100

3.4

PrimateAI

Uncertain

0.65

PROVEAN

Uncertain

-3.4

D;D;D

REVEL

Benign

0.25

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.88

P;.;.

Vest4

0.48

MutPred

0.71

Gain of ubiquitination at E121 (P = 0.0177);Gain of ubiquitination at E121 (P = 0.0177);Gain of ubiquitination at E121 (P = 0.0177);

MVP

0.60

MPC

0.58

ClinPred

0.99

GERP RS

4.8

Varity_R

0.61

gMVP

0.62

Mutation Taster

=72/28

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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rs1303461267

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over