Genetic Variant ZSCAN22:p.Ser226Leu (chr19-58338527-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001321117.2(ZSCAN22):c.661C>T(p.Arg221*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000353 in 1,614,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

ZSCAN22
NM_001321117.2 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.934

Publications

0 publications found

Variant links:

Genes affected

ZSCAN22 (HGNC:4929): (zinc finger and SCAN domain containing 22) 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]

ZSCAN22 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP6

Variant 19-58338527-C-T is Benign according to our data. Variant chr19-58338527-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3823644.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321117.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSCAN22	NM_181846.3	MANE Select	c.677C>T	p.Ser226Leu	missense	Exon 3 of 3	NP_862829.1	P10073
ZSCAN22	NM_001321117.2		c.661C>T	p.Arg221*	stop_gained	Exon 3 of 3	NP_001308046.1
ZSCAN22	NM_001321116.2		c.677C>T	p.Ser226Leu	missense	Exon 3 of 3	NP_001308045.1	P10073

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSCAN22	ENST00000329665.5	TSL:1 MANE Select	c.677C>T	p.Ser226Leu	missense	Exon 3 of 3	ENSP00000332433.3	P10073
ZSCAN22	ENST00000850584.1		c.677C>T	p.Ser226Leu	missense	Exon 3 of 3	ENSP00000520871.1	P10073
ZSCAN22	ENST00000904370.1		c.677C>T	p.Ser226Leu	missense	Exon 3 of 3	ENSP00000574429.1

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000795

AC:

AN:

251472

AF XY:

0.000110

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.0000867

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000335

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000440

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.0000671

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.000267

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000899

AC:

AN:

1112012

Other (OTH)

AF:

0.0000662

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.0000525

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000144

AC:

AN:

41564

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68034

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000579

Hom.:

Bravo

AF:

0.000106

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000107

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.51

(source)

DANN

Benign

0.24

DEOGEN2

Benign

0.017

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0072

LIST_S2

Benign

0.19

M_CAP

Benign

0.0057

MetaRNN

Benign

0.026

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.20

PhyloP100

-0.93

PrimateAI

Benign

0.22

PROVEAN

Benign

-0.64

REVEL

Benign

0.022

Sift

Benign

0.49

Sift4G

Benign

0.52

Polyphen

0.0

Vest4

0.050

MVP

0.099

MPC

0.094

ClinPred

0.011

GERP RS

0.083

Varity_R

0.030

gMVP

0.032

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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