6-28575510-G-C

Position:

• chr6-28575510-G-C

Variant summary

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

The NM_052923.2(SCAND3):​c.1195C>G​(p.Leu399Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,572 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: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SCAND3 NM_052923.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.355

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=0.17856914).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCAND3	NM_052923.2	c.1195C>G	p.Leu399Val	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.1195C>G	p.Leu399Val	missense_variant	3/4	1	NM_052923.2	ENSP00000395259.2
SCAND3	ENST00000646382.1	c.742C>G	p.Leu248Val	missense_variant	4/5			ENSP00000494942.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461572 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 727084

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: 0.00000360

Gnomad4 OTH exome AF: 0.00

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

Sep 25, 2023

The c.1195C>G (p.L399V) alteration is located in exon 3 (coding exon 3) of the ZBED9 gene. This alteration results from a C to G substitution at nucleotide position 1195, causing the leucine (L) at amino acid position 399 to be replaced by a valine (V). 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	0.12
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.1
DANN	Benign	0.95
DEOGEN2	Benign	0.027	.;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	.;L
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.26	.;N
REVEL	Benign	0.027
Sift	Benign	0.22	.;T
Sift4G	Benign	0.14	.;T
Polyphen		0.043	.;B
Vest4		0.20
MutPred		0.65		.;Gain of methylation at K402 (P = 0.0854);
MVP		0.33
MPC		0.38
ClinPred		0.076	T
GERP RS		0.63
Varity_R		0.071
gMVP		0.39

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.

Other links and lift over

hg19: chr6-28543287;