rs10883942

Variant names:

• chr10-103891628-T-C
• rs10883942
• NM_024928.5:c.876+502A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024928.5(STN1):​c.876+502A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 152,106 control chromosomes in the GnomAD database, including 15,763 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 0.44 (15763 hom., cov: 33)
• Consequence: STN1 NM_024928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.72
• Publications: 8 publications found

Genes affected

STN1 (HGNC:26200): (STN1 subunit of CST complex) OBFC1 and C17ORF68 (MIM 613129) are subunits of an alpha accessory factor (AAF) that stimulates the activity of DNA polymerase-alpha-primase (see MIM 176636), the enzyme that initiates DNA replication (Casteel et al., 2009 [PubMed 19119139]). OBFC1 also appears to function in a telomere-associated complex with C17ORF68 and TEN1 (C17ORF106; MIM 613130) (Miyake et al., 2009 [PubMed 19854130]).[supplied by OMIM, Nov 2009]

STN1 Gene-Disease associations (from GenCC):

• cerebroretinal microangiopathy with calcifications and cysts 2

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Ambry Genetics, Genomics England PanelApp
• Coats plus syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000289744 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024928.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STN1	NM_024928.5	MANE Select	c.876+502A>G		intron	N/A	NP_079204.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STN1	ENST00000224950.8	TSL:1 MANE Select	c.876+502A>G		intron	N/A	ENSP00000224950.3
	STN1	ENST00000698305.1		c.876+502A>G		intron	N/A	ENSP00000513665.1
	STN1	ENST00000369764.2	TSL:2	c.876+502A>G		intron	N/A	ENSP00000358779.1

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67667 AN: 151988 Hom.: 15757 Cov.: 33

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.459

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.445 AC: 67683 AN: 152106 Hom.: 15763 Cov.: 33 AF XY: 0.449 AC XY: 33371 AN XY: 74328

African (AFR) AF: 0.315 AC: 13073 AN: 41482

American (AMR) AF: 0.496 AC: 7588 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1375 AN: 3468

East Asian (EAS) AF: 0.344 AC: 1783 AN: 5186

South Asian (SAS) AF: 0.403 AC: 1942 AN: 4818

European-Finnish (FIN) AF: 0.599 AC: 6336 AN: 10576

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.497 AC: 33786 AN: 67972

Other (OTH) AF: 0.457 AC: 965 AN: 2112

Alfa AF: 0.460 Hom.: 2742

Bravo AF: 0.433

Asia WGS AF: 0.366 AC: 1277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.62
DANN	Benign	0.35
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs10883942; hg19: chr10-105651386;