6-28575792-C-T

Position:

• chr6-28575792-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052923.2(SCAND3):​c.913G>A​(p.Glu305Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCAND3 NM_052923.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.63

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]

ACMG classification

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=0.2604146).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAND3	NM_052923.2	c.913G>A	p.Glu305Lys	missense_variant	3/4	ENST00000452236.3	NP_443155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCAND3	ENST00000452236.3	c.913G>A	p.Glu305Lys	missense_variant	3/4	1	NM_052923.2	ENSP00000395259.2
SCAND3	ENST00000646382.1	c.460G>A	p.Glu154Lys	missense_variant	4/5			ENSP00000494942.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 06, 2023

The c.913G>A (p.E305K) alteration is located in exon 3 (coding exon 3) of the ZBED9 gene. This alteration results from a G to A substitution at nucleotide position 913, causing the glutamic acid (E) at amino acid position 305 to be replaced by a lysine (K). 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	Uncertain	0.49
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	23
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.025	.;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Benign	0.61	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.26	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	1.9	.;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-0.51	.;N
REVEL	Benign	0.097
Sift	Uncertain	0.0030	.;D
Sift4G	Uncertain	0.0040	.;D
Polyphen		0.98	.;D
Vest4		0.36
MutPred		0.43		.;Gain of helix (P = 0.0128);
MVP		0.45
MPC		0.43
ClinPred		0.67	D
GERP RS		2.8
Varity_R		0.16
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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.

Other links and lift over

hg19: chr6-28543569;