10-103916188-T-C

Variant names:

• chr10-103916188-T-C
• rs9419958
• NM_024928.5:c.133+1274A>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.133+1274A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.758 in 152,160 control chromosomes in the GnomAD database, including 46,218 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 0.76 (46218 hom., cov: 33)
• Consequence: STN1 NM_024928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.78
• Publications: 73 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 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.133+1274A>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.133+1274A>G		intron	N/A	ENSP00000224950.3	Q9H668
	STN1	ENST00000698305.1		c.133+1274A>G		intron	N/A	ENSP00000513665.1	A0A8V8TM56
	STN1	ENST00000369764.2	TSL:2	c.133+1274A>G		intron	N/A	ENSP00000358779.1	Q9H668

Frequencies

GnomAD3 genomes AF: 0.758 AC: 115294 AN: 152042 Hom.: 46212 Cov.: 33

Gnomad AFR AF: 0.472

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.900

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.780

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

GnomAD4 genome AF: 0.758 AC: 115325 AN: 152160 Hom.: 46218 Cov.: 33 AF XY: 0.765 AC XY: 56884 AN XY: 74390

African (AFR) AF: 0.472 AC: 19553 AN: 41442

American (AMR) AF: 0.850 AC: 13006 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2855 AN: 3472

East Asian (EAS) AF: 0.986 AC: 5121 AN: 5192

South Asian (SAS) AF: 0.901 AC: 4354 AN: 4830

European-Finnish (FIN) AF: 0.881 AC: 9335 AN: 10598

Middle Eastern (MID) AF: 0.803 AC: 236 AN: 294

European-Non Finnish (NFE) AF: 0.858 AC: 58360 AN: 68010

Other (OTH) AF: 0.775 AC: 1639 AN: 2114

Alfa AF: 0.825 Hom.: 154840

Bravo AF: 0.744

Asia WGS AF: 0.870 AC: 3026 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.8
DANN	Benign	0.75
PhyloP100		-1.8
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: rs9419958; hg19: chr10-105675946;