10-103884978-T-G

Variant names:

• chr10-103884978-T-G
• rs4918068
• NM_024928.5:c.950-2137A>C

Variant summary

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

The NM_024928.5(STN1):​c.950-2137A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,944 control chromosomes in the GnomAD database, including 15,721 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 (15721 hom., cov: 31)
• Consequence: STN1 NM_024928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28
• Publications: 7 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.492 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.950-2137A>C		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.950-2137A>C		intron	N/A	ENSP00000224950.3	Q9H668
	STN1	ENST00000698245.1		c.*2647A>C		3_prime_UTR	Exon 10 of 10	ENSP00000513626.1	A0A8V8TNB0
	STN1	ENST00000698305.1		c.950-2116A>C		intron	N/A	ENSP00000513665.1	A0A8V8TM56

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67517 AN: 151824 Hom.: 15714 Cov.: 31

Gnomad AFR AF: 0.314

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.343

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.444 AC: 67535 AN: 151944 Hom.: 15721 Cov.: 31 AF XY: 0.448 AC XY: 33293 AN XY: 74262

African (AFR) AF: 0.314 AC: 12995 AN: 41430

American (AMR) AF: 0.497 AC: 7593 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1375 AN: 3470

East Asian (EAS) AF: 0.342 AC: 1765 AN: 5156

South Asian (SAS) AF: 0.403 AC: 1938 AN: 4812

European-Finnish (FIN) AF: 0.599 AC: 6318 AN: 10542

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

European-Non Finnish (NFE) AF: 0.497 AC: 33757 AN: 67962

Other (OTH) AF: 0.456 AC: 960 AN: 2106

Alfa AF: 0.345 Hom.: 1034

Bravo AF: 0.433

Asia WGS AF: 0.366 AC: 1275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	6.3
DANN	Benign	0.78
PhyloP100		1.3
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: rs4918068; hg19: chr10-105644736;