6-28575460-C-G

Variant names:

• chr6-28575460-C-G
• rs141691229
• NM_052923.2:c.1245G>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_052923.2(SCAND3):​c.1245G>C​(p.Thr415Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.002 in 1,613,682 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0078 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (17 hom.)
• Consequence: SCAND3 NM_052923.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00776 (1181/152230) while in subpopulation AFR AF= 0.0265 (1100/41536). AF 95% confidence interval is 0.0252. There are 12 homozygotes in gnomad4. There are 531 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCAND3	NM_052923.2	c.1245G>C	p.Thr415Thr	synonymous_variant	Exon 3 of 4	ENST00000452236.3	NP_443155.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCAND3	ENST00000452236.3	c.1245G>C	p.Thr415Thr	synonymous_variant	Exon 3 of 4	1	NM_052923.2	ENSP00000395259.2
SCAND3	ENST00000646382.1	c.792G>C	p.Thr264Thr	synonymous_variant	Exon 4 of 5			ENSP00000494942.1

Frequencies

GnomAD3 genomes AF: 0.00775 AC: 1179 AN: 152112 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.0265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000706

Gnomad OTH AF: 0.00384

GnomAD3 exomes AF: 0.00224 AC: 559 AN: 249918 Hom.: 3 AF XY: 0.00169 AC XY: 229 AN XY: 135486

Gnomad AFR exome AF: 0.0275

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.000696

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000610

Gnomad OTH exome AF: 0.000988

GnomAD4 exome AF: 0.00140 AC: 2044 AN: 1461452 Hom.: 17 Cov.: 34 AF XY: 0.00128 AC XY: 934 AN XY: 727046

Gnomad4 AFR exome AF: 0.0284

Gnomad4 AMR exome AF: 0.00172

Gnomad4 ASJ exome AF: 0.000727

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.000789

Gnomad4 OTH exome AF: 0.00184

GnomAD4 genome AF: 0.00776 AC: 1181 AN: 152230 Hom.: 12 Cov.: 32 AF XY: 0.00713 AC XY: 531 AN XY: 74428

Gnomad4 AFR AF: 0.0265

Gnomad4 AMR AF: 0.00150

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000706

Gnomad4 OTH AF: 0.00380

Alfa AF: 0.000732 Hom.: 0

Bravo AF: 0.00901

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000709

EpiControl AF: 0.000652

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.37
DANN	Benign	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

LitVar

Other links and lift over

dbSNP: rs141691229; hg19: chr6-28543237;