Variant 6-28129780-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025231.3(ZSCAN16):c.877A>C(p.Lys293Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000848 in 1,614,038 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00043 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00089 ( 1 hom. )

Consequence

ZSCAN16
NM_025231.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.35

Variant links:

Genes affected

ZSCAN16 (HGNC:20813): (zinc finger and SCAN domain containing 16) Enables sequence-specific double-stranded 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]

ZSCAN16 links:

ZSCAN16-AS1 (HGNC:48982): (ZSCAN16 antisense RNA 1)

ZSCAN16-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02813068).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZSCAN16	NM_025231.3 linkuse as main transcript	c.877A>C	p.Lys293Gln	missense_variant	4/4	ENST00000340487.5
ZSCAN16-AS1	NR_103456.1 linkuse as main transcript	n.573-6569T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZSCAN16	ENST00000340487.5 linkuse as main transcript	c.877A>C	p.Lys293Gln	missense_variant	4/4	1	NM_025231.3	P1
ZSCAN16-AS1	ENST00000660873.1 linkuse as main transcript	n.77+6965T>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000427

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.000838

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000310

AC:

AN:

251264

Hom.:

AF XY:

0.000287

AC XY:

AN XY:

135798

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000634

Gnomad OTH exome

AF:

0.000653

GnomAD4 exome

AF:

0.000891

AC:

1303

AN:

1461836

Hom.:

Cov.:

AF XY:

0.000825

AC XY:

600

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00110

Gnomad4 OTH exome

AF:

0.00131

GnomAD4 genome

AF:

0.000427

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000838

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000666

Hom.:

Bravo

AF:

0.000514

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00163

AC:

ExAC

AF:

0.000346

AC:

EpiCase

AF:

0.00125

EpiControl

AF:

0.000474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 11, 2021

The c.877A>C (p.K293Q) alteration is located in exon 4 (coding exon 3) of the ZSCAN16 gene. This alteration results from a A to C substitution at nucleotide position 877, causing the lysine (K) at amino acid position 293 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.038

Eigen

Benign

-0.81

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.076

LIST_S2

Benign

0.26

M_CAP

Benign

0.0027

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.38

PROVEAN

Benign

0.28

REVEL

Benign

0.036

Sift

Benign

1.0

Sift4G

Benign

0.58

Polyphen

0.21

Vest4

0.075

MVP

0.24

MPC

0.54

ClinPred

0.030

GERP RS

0.92

Varity_R

0.033

gMVP

0.022

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over