dbSNP rs776048732: ZSCAN10:p.Arg707Leu (chr16-3089314-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_032805.3(ZSCAN10):c.2120G>T(p.Arg707Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000141 in 1,421,492 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R707Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ZSCAN10
NM_032805.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0370

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.36973697).

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.2120G>T	p.Arg707Leu	missense	Exon 6 of 6	NP_116194.2	Q96SZ4-1
ZSCAN10	NM_001282416.2		c.1709G>T	p.Arg570Leu	missense	Exon 5 of 5	NP_001269345.1	Q96SZ4-3
ZSCAN10	NM_001365272.1		c.1574G>T	p.Arg525Leu	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.2120G>T	p.Arg707Leu	missense	Exon 6 of 6	ENSP00000458879.2	I3L1J3
ZSCAN10	ENST00000252463.6	TSL:1	c.1955G>T	p.Arg652Leu	missense	Exon 5 of 5	ENSP00000252463.2	A0ABB0GZV6
ZSCAN10	ENST00000538082.5	TSL:4	c.1709G>T	p.Arg570Leu	missense	Exon 5 of 5	ENSP00000440047.2	Q96SZ4-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000141

AC:

AN:

1421492

Hom.:

Cov.:

AF XY:

0.00000142

AC XY:

AN XY:

705448

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32292

American (AMR)

AF:

0.00

AC:

AN:

41128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24190

East Asian (EAS)

AF:

0.00

AC:

AN:

39196

South Asian (SAS)

AF:

0.00

AC:

AN:

81810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39730

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5626

European-Non Finnish (NFE)

AF:

0.00000182

AC:

AN:

1098472

Other (OTH)

AF:

0.00

AC:

AN:

59048

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

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.044

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.14

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.046

MetaRNN

Benign

0.37

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.1

PhyloP100

0.037

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.17

Sift

Benign

0.068

Sift4G

Benign

0.072

Polyphen

0.99

Vest4

0.53

MutPred

0.39

Loss of MoRF binding (P = 0.0352)

MVP

0.55

MPC

1.8

ClinPred

0.97

GERP RS

4.4

Varity_R

0.18

gMVP

0.72

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over