Variant chr6-28575155-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_052923.2(SCAND3):c.1550C>T(p.Thr517Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,986 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

SCAND3
NM_052923.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.148

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 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=0.08499172).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAND3	NM_052923.2 linkuse as main transcript	c.1550C>T	p.Thr517Ile	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.1550C>T	p.Thr517Ile	missense_variant	3/4	1	NM_052923.2	ENSP00000395259.2		Q6R2W3
SCAND3	ENST00000646382.1 linkuse as main transcript	c.1097C>T	p.Thr366Ile	missense_variant	4/5			ENSP00000494942.1		A0A2R8Y5N3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000599

AC:

AN:

250240

Hom.:

AF XY:

0.0000887

AC XY:

AN XY:

135264

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000145

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:

0.0000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000383

AC:

AN:

1461770

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000134

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:

0.0000441

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000847

Hom.:

Bravo

AF:

0.0000642

ExAC

AF:

0.0000824

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

Sep 11, 2024

The c.1550C>T (p.T517I) alteration is located in exon 3 (coding exon 3) of the ZBED9 gene. This alteration results from a C to T substitution at nucleotide position 1550, causing the threonine (T) at amino acid position 517 to be replaced by an isoleucine (I). 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

0.10

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.12

.;T

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.085

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

.;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.66

.;N

REVEL

Benign

0.069

Sift

Benign

0.13

.;T

Sift4G

Benign

0.10

.;T

Polyphen

0.0010

.;B

Vest4

0.099

MutPred

0.66

.;Loss of phosphorylation at T517 (P = 0.0557);

MVP

0.39

MPC

0.37

ClinPred

0.018

GERP RS

0.16

Varity_R

0.039

gMVP

0.75

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