10-103909864-T-C

Variant names:

• chr10-103909864-T-C
• rs12765878
• NM_024928.5:c.229+663A>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.229+663A>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 151,986 control chromosomes in the GnomAD database, including 15,752 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 0.45 (15752 hom., cov: 31)
• Consequence: STN1 NM_024928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.140
• Publications: 27 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: Ambry Genetics, Genomics England PanelApp, PanelApp Australia, G2P
• 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=-0.99).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STN1	NM_024928.5	MANE Select	c.229+663A>G		intron	N/A	NP_079204.2	Q9H668

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STN1	ENST00000224950.8	TSL:1 MANE Select	c.229+663A>G		intron	N/A	ENSP00000224950.3	Q9H668
	STN1	ENST00000698305.1		c.229+663A>G		intron	N/A	ENSP00000513665.1	A0A8V8TM56
	STN1	ENST00000369764.2	TSL:2	c.229+663A>G		intron	N/A	ENSP00000358779.1	Q9H668

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67627 AN: 151868 Hom.: 15747 Cov.: 31

Gnomad AFR AF: 0.316

Gnomad AMI AF: 0.777

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: 67643 AN: 151986 Hom.: 15752 Cov.: 31 AF XY: 0.449 AC XY: 33353 AN XY: 74290

African (AFR) AF: 0.316 AC: 13090 AN: 41450

American (AMR) AF: 0.497 AC: 7592 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1374 AN: 3472

East Asian (EAS) AF: 0.343 AC: 1769 AN: 5156

South Asian (SAS) AF: 0.402 AC: 1937 AN: 4816

European-Finnish (FIN) AF: 0.599 AC: 6316 AN: 10550

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

European-Non Finnish (NFE) AF: 0.497 AC: 33768 AN: 67944

Other (OTH) AF: 0.457 AC: 963 AN: 2108

Alfa AF: 0.457 Hom.: 3075

Bravo AF: 0.433

Asia WGS AF: 0.367 AC: 1278 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	3.6
DANN	Benign	0.70
PhyloP100		-0.14
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: rs12765878; hg19: chr10-105669622;