6-28574703-G-T

Position:

• chr6-28574703-G-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.2002C>A​(p.Pro668Thr) 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 1,461,792 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: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCAND3 NM_052923.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.292

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=0.11509186).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAND3	NM_052923.2	c.2002C>A	p.Pro668Thr	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.2002C>A	p.Pro668Thr	missense_variant	3/4	1	NM_052923.2	ENSP00000395259.2
SCAND3	ENST00000646382.1	c.1549C>A	p.Pro517Thr	missense_variant	4/5			ENSP00000494942.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461792 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 727194

Gnomad4 AFR exome AF: 0.0000299

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: 0.00

GnomAD4 genome Cov.: 33

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Sep 01, 2021

The c.2002C>A (p.P668T) 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 2002, causing the proline (P) at amino acid position 668 to be replaced by a threonine (T). 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	0.080
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	18
DANN	Benign	0.85
DEOGEN2	Benign	0.024	.;T
Eigen	Benign	0.048
Eigen_PC	Benign	-0.0099
FATHMM_MKL	Benign	0.069	N
LIST_S2	Benign	0.52	T;T
M_CAP	Benign	0.0064	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-0.75	T
MutationAssessor	Benign	0.20	.;N
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.84	.;N
REVEL	Benign	0.062
Sift	Benign	0.19	.;T
Sift4G	Benign	0.36	.;T
Polyphen		0.99	.;D
Vest4		0.15
MutPred		0.20		.;Gain of phosphorylation at P668 (P = 0.0306);
MVP		0.31
MPC		0.39
ClinPred		0.17	T
GERP RS		2.5
Varity_R		0.074
gMVP		0.40

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

Other links and lift over

dbSNP: rs1764328933; hg19: chr6-28542480;