Genetic Variant ZSCAN10:p.Ala749Thr (chr16-3089189-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032805.3(ZSCAN10):c.2245G>A(p.Ala749Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000634 in 1,577,022 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict 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. A749S) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000056 ( 0 hom. )

Consequence

ZSCAN10
NM_032805.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.06

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1329779).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZSCAN10	NM_032805.3 link	c.2245G>A	p.Ala749Thr	missense_variant	Exon 6 of 6	ENST00000576985.6	NP_116194.2	Q96SZ4I3L1J3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
ZSCAN10	ENST00000576985.6 link	c.2245G>A	p.Ala749Thr	missense_variant	Exon 6 of 6	5	NM_032805.3	ENSP00000458879.2	I3L1J3
ZSCAN10	ENST00000252463.6 link	c.2080G>A	p.Ala694Thr	missense_variant	Exon 5 of 5	1		ENSP00000252463.2	Q96SZ4-1
ZSCAN10	ENST00000538082.5 link	c.1834G>A	p.Ala612Thr	missense_variant	Exon 5 of 5	4		ENSP00000440047.2	Q96SZ4-3
ZSCAN10	ENST00000575108.5 link	c.1063G>A	p.Ala355Thr	missense_variant	Exon 5 of 5	2		ENSP00000459520.1	Q96SZ4-2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000154

AC:

AN:

194582

Hom.:

AF XY:

0.0000186

AC XY:

AN XY:

107684

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 SAS exome

AF:

0.0000388

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000229

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000561

AC:

AN:

1424804

Hom.:

Cov.:

AF XY:

0.00000424

AC XY:

AN XY:

707910

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000258

Gnomad4 SAS exome

AF:

0.0000122

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000545

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000250

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.012

T;T;.;.

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.85

D;D;D;D

M_CAP

Benign

0.0075

MetaRNN

Benign

0.13

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.82

.;L;.;.

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.92

.;N;.;.

REVEL

Benign

0.086

Sift

Benign

0.15

.;T;.;.

Sift4G

Benign

0.097

T;T;D;D

Polyphen

0.21, 1.0

.;B;D;.

Vest4

0.22

MutPred

0.44

.;Gain of disorder (P = 0.0866);.;.;

MVP

0.48

MPC

1.1

ClinPred

0.37

GERP RS

4.0

Varity_R

0.076

gMVP

0.15

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over