Genetic Variant ZSCAN10:p.Arg741Gln (chr16-3089212-C-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_032805.3(ZSCAN10):c.2222G>A(p.Arg741Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000602 in 1,579,368 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

ZSCAN10
NM_032805.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.865

Publications

0 publications found

Variant links:

Genes affected

ZSCAN10 (HGNC:12997): (zinc finger and SCAN domain containing 10) 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 negative regulation of transcription, DNA-templated and regulation of transcription by RNA polymerase II. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZSCAN10 Gene-Disease associations (from GenCC):

otofacial neurodevelopmental syndrome
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ZSCAN10 links:

Genome browser will be placed here

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=0.15577328).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032805.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSCAN10	NM_032805.3	MANE Select	c.2222G>A	p.Arg741Gln	missense	Exon 6 of 6	NP_116194.2	Q96SZ4-1
ZSCAN10	NM_001282416.2		c.1811G>A	p.Arg604Gln	missense	Exon 5 of 5	NP_001269345.1	Q96SZ4-3
ZSCAN10	NM_001365272.1		c.1676G>A	p.Arg559Gln	missense	Exon 5 of 5	NP_001352201.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZSCAN10	ENST00000576985.6	TSL:5 MANE Select	c.2222G>A	p.Arg741Gln	missense	Exon 6 of 6	ENSP00000458879.2	I3L1J3
ZSCAN10	ENST00000252463.6	TSL:1	c.2057G>A	p.Arg686Gln	missense	Exon 5 of 5	ENSP00000252463.2	A0ABB0GZV6
ZSCAN10	ENST00000538082.5	TSL:4	c.1811G>A	p.Arg604Gln	missense	Exon 5 of 5	ENSP00000440047.2	Q96SZ4-3

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

GnomAD2 exomes

AF:

0.0000249

AC:

AN:

200618

AF XY:

0.0000270

show subpopulations

Gnomad AFR exome

AF:

0.0000812

Gnomad AMR exome

AF:

0.0000319

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000335

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000603

AC:

AN:

1427160

Hom.:

Cov.:

AF XY:

0.0000479

AC XY:

AN XY:

709628

show subpopulations

African (AFR)

AF:

0.0000311

AC:

AN:

32140

American (AMR)

AF:

0.0000239

AC:

AN:

41822

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25098

East Asian (EAS)

AF:

0.00

AC:

AN:

37966

South Asian (SAS)

AF:

0.00

AC:

AN:

83192

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5392

European-Non Finnish (NFE)

AF:

0.0000762

AC:

AN:

1102248

Other (OTH)

AF:

0.00

AC:

AN:

59218

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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:

0.0000591

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74442

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41528

American (AMR)

AF:

0.00

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

67984

Other (OTH)

AF:

0.00

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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:

0.00

Hom.:

Bravo

AF:

0.0000340

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.0000250

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

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

Pathogenic

0.88

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.0085

Eigen

Benign

0.071

Eigen_PC

Benign

0.028

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.022

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.93

PhyloP100

-0.86

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

0.060

REVEL

Benign

0.16

Sift

Benign

0.32

Sift4G

Benign

0.62

Polyphen

1.0

Vest4

0.32

MVP

0.74

MPC

2.0

ClinPred

0.30

GERP RS

4.7

Varity_R

0.089

gMVP

0.80

Mutation Taster

=95/5

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