chr19-58085053-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_001145543.2(ZSCAN18):c.1165G>A(p.Gly389Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000425 in 1,598,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

ZSCAN18
NM_001145543.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -4.06

Publications

2 publications found

Variant links:

Genes affected

ZSCAN18 (HGNC:21037): (zinc finger and SCAN domain containing 18) 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]

ZSCAN18 links:

ZNF135 (HGNC:12919): (zinc finger protein 135) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in cytoskeleton organization and regulation of cell morphogenesis. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZNF135 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=0.07817155).

BP6

Variant 19-58085053-C-T is Benign according to our data. Variant chr19-58085053-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2204770.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145543.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSCAN18	NM_001145543.2	MANE Select	c.1165G>A	p.Gly389Ser	missense	Exon 7 of 7	NP_001139015.1	Q8TBC5-1
ZSCAN18	NM_001145542.1		c.1333G>A	p.Gly445Ser	missense	Exon 7 of 7	NP_001139014.1	Q8TBC5-3
ZSCAN18	NM_023926.5		c.1165G>A	p.Gly389Ser	missense	Exon 7 of 7	NP_076415.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSCAN18	ENST00000601144.6	TSL:1 MANE Select	c.1165G>A	p.Gly389Ser	missense	Exon 7 of 7	ENSP00000468934.1	Q8TBC5-1
ZSCAN18	ENST00000240727.10	TSL:1	c.1165G>A	p.Gly389Ser	missense	Exon 7 of 7	ENSP00000240727.5	Q8TBC5-1
ZSCAN18	ENST00000433686.6	TSL:1	c.856G>A	p.Gly286Ser	missense	Exon 6 of 6	ENSP00000412253.2	A0A0C4DG78

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

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:

0.0000588

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.0000302

AC:

AN:

231826

AF XY:

0.0000315

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:

0.0000993

Gnomad NFE exome

AF:

0.0000484

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000387

AC:

AN:

1446422

Hom.:

Cov.:

AF XY:

0.0000307

AC XY:

AN XY:

717602

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33060

American (AMR)

AF:

0.0000459

AC:

AN:

43558

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25362

East Asian (EAS)

AF:

0.00

AC:

AN:

39358

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84552

European-Finnish (FIN)

AF:

0.0000582

AC:

AN:

51568

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5704

European-Non Finnish (NFE)

AF:

0.0000417

AC:

AN:

1103700

Other (OTH)

AF:

0.0000672

AC:

AN:

59560

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.0000789

AC:

AN:

152168

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41450

American (AMR)

AF:

0.000327

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68002

Other (OTH)

AF:

0.000957

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.000144

Hom.:

Bravo

AF:

0.000113

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

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

0.11

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.12

(source)

DANN

Benign

0.79

DEOGEN2

Benign

0.0091

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.40

M_CAP

Benign

0.0019

MetaRNN

Benign

0.078

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.20

PhyloP100

-4.1

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.0040

Sift

Benign

0.038

Sift4G

Benign

0.37

Polyphen

0.0

Vest4

0.12

MVP

0.082

MPC

0.061

ClinPred

0.032

GERP RS

-3.2

Varity_R

0.028

gMVP

0.18

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