10-103884565-G-C

Variant names:

• chr10-103884565-G-C
• rs10786774
• NM_024928.5:c.950-1724C>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.950-1724C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.903 in 152,252 control chromosomes in the GnomAD database, including 62,140 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 0.90 (62140 hom., cov: 32)
• Consequence: STN1 NM_024928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.987
• Publications: 6 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=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 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.950-1724C>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.950-1724C>G		intron	N/A	ENSP00000224950.3
	STN1	ENST00000698245.1		c.*3060C>G		3_prime_UTR	Exon 10 of 10	ENSP00000513626.1
	STN1	ENST00000698305.1		c.950-1703C>G		intron	N/A	ENSP00000513665.1

Frequencies

GnomAD3 genomes AF: 0.903 AC: 137319 AN: 152134 Hom.: 62084 Cov.: 32

Gnomad AFR AF: 0.866

Gnomad AMI AF: 0.953

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.915

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.900

Gnomad OTH AF: 0.910

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

GnomAD4 genome AF: 0.903 AC: 137434 AN: 152252 Hom.: 62140 Cov.: 32 AF XY: 0.906 AC XY: 67429 AN XY: 74434

African (AFR) AF: 0.866 AC: 35970 AN: 41518

American (AMR) AF: 0.942 AC: 14415 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.915 AC: 3178 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5185 AN: 5186

South Asian (SAS) AF: 0.982 AC: 4738 AN: 4826

European-Finnish (FIN) AF: 0.912 AC: 9665 AN: 10600

Middle Eastern (MID) AF: 0.922 AC: 271 AN: 294

European-Non Finnish (NFE) AF: 0.900 AC: 61219 AN: 68022

Other (OTH) AF: 0.911 AC: 1924 AN: 2112

Alfa AF: 0.900 Hom.: 7650

Bravo AF: 0.903

Asia WGS AF: 0.982 AC: 3413 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	6.0
DANN	Benign	0.31
PhyloP100		0.99
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: rs10786774; hg19: chr10-105644323;