6-28575294-T-A

Variant names:

• chr6-28575294-T-A
• rs1168506788
• NM_052923.2:c.1411A>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_052923.2(SCAND3):​c.1411A>T​(p.Ser471Cys) 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 1,461,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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: 0.130
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36654282).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052923.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAND3	NM_052923.2	MANE Select	c.1411A>T	p.Ser471Cys	missense	Exon 3 of 4	NP_443155.1	Q6R2W3
	SCAND3	NM_001329616.2		c.958A>T	p.Ser320Cys	missense	Exon 5 of 6	NP_001316545.1	A0A2R8Y5N3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCAND3	ENST00000452236.3	TSL:1 MANE Select	c.1411A>T	p.Ser471Cys	missense	Exon 3 of 4	ENSP00000395259.2	Q6R2W3
	SCAND3	ENST00000646382.1		c.958A>T	p.Ser320Cys	missense	Exon 4 of 5	ENSP00000494942.1	A0A2R8Y5N3
	SCAND3	ENST00000927696.1		c.421-1467A>T		intron	N/A	ENSP00000597755.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461706 Hom.: 0 Cov.: 35 AF XY: 0.00000413 AC XY: 3 AN XY: 727150

African (AFR) AF: 0.0000299 AC: 1 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.91
DEOGEN2	Benign	0.031	T
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.44
FATHMM_MKL	Benign	0.030	N
LIST_S2	Benign	0.39	T
M_CAP	Benign	0.0074	T
MetaRNN	Benign	0.37	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.13
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.15	N
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.015	D
Polyphen		0.94	P
Vest4		0.29
MutPred		0.81		Loss of helix (P = 0.0558)
MVP		0.47
MPC		0.67
ClinPred		0.39	T
GERP RS		2.0
Varity_R		0.13
gMVP		0.43
Mutation Taster		=86/14	polymorphism

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

Other links and lift over

dbSNP: rs1168506788; hg19: chr6-28543071;