Variant chr6-28575239-G-T 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_052923.2(SCAND3):c.1466C>A(p.Thr489Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,724 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SCAND3
NM_052923.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.773

Variant links:

Genes affected

SCAND3 (HGNC:13851): (SCAN domain containing 3) Predicted to enable nucleic acid binding activity. Involved in positive regulation of cell cycle and positive regulation of epithelial cell proliferation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SCAND3 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=0.042130142).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAND3	NM_052923.2 linkuse as main transcript	c.1466C>A	p.Thr489Asn	missense_variant	3/4	ENST00000452236.3	NP_443155.1	Q6R2W3A0A1U9X8W9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAND3	ENST00000452236.3 linkuse as main transcript	c.1466C>A	p.Thr489Asn	missense_variant	3/4	1	NM_052923.2	ENSP00000395259.2		Q6R2W3
SCAND3	ENST00000646382.1 linkuse as main transcript	c.1013C>A	p.Thr338Asn	missense_variant	4/5			ENSP00000494942.1		A0A2R8Y5N3

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152196

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461724

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727162

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000657

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Mar 22, 2023

The c.1466C>A (p.T489N) alteration is located in exon 3 (coding exon 3) of the ZBED9 gene. This alteration results from a C to A substitution at nucleotide position 1466, causing the threonine (T) at amino acid position 489 to be replaced by an asparagine (N). 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

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.023

.;T

Eigen

Benign

-0.73

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.66

T;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.042

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

.;L

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.15

.;N

REVEL

Benign

0.0070

Sift

Benign

0.099

.;T

Sift4G

Uncertain

0.014

.;D

Polyphen

0.047

.;B

Vest4

0.21

MutPred

0.32

.;Gain of MoRF binding (P = 0.1283);

MVP

0.22

MPC

0.41

ClinPred

0.057

GERP RS

1.4

Varity_R

0.051

gMVP

0.30

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over