6-28575354-T-G

Variant names:

• chr6-28575354-T-G
• NM_052923.2:c.1351A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_052923.2(SCAND3):​c.1351A>C​(p.Ser451Arg) 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. 14/22 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)
• Consequence: SCAND3 NM_052923.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.34
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13945207).

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.1351A>C	p.Ser451Arg	missense	Exon 3 of 4	NP_443155.1	Q6R2W3
	SCAND3	NM_001329616.2		c.898A>C	p.Ser300Arg	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.1351A>C	p.Ser451Arg	missense	Exon 3 of 4	ENSP00000395259.2	Q6R2W3
	SCAND3	ENST00000646382.1		c.898A>C	p.Ser300Arg	missense	Exon 4 of 5	ENSP00000494942.1	A0A2R8Y5N3
	SCAND3	ENST00000927696.1		c.421-1527A>C		intron	N/A	ENSP00000597755.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

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	Uncertain	0.53
BayesDel_addAF	Benign	-0.038	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.84	L
PhyloP100		1.3
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.46	N
REVEL	Benign	0.23
Sift	Benign	0.15	T
Sift4G	Uncertain	0.034	D
Polyphen		0.62	P
Vest4		0.55
MutPred		0.60		Gain of catalytic residue at S451 (P = 0.0219)
MVP		0.44
MPC		0.53
ClinPred		0.15	T
GERP RS		1.8
Varity_R		0.080
gMVP		0.49
Mutation Taster		=89/11	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

hg19: chr6-28543131;