10-103915096-A-G

Variant names:

• chr10-103915096-A-G
• rs1265164
• NM_024928.5:c.133+2366T>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.133+2366T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 152,128 control chromosomes in the GnomAD database, including 46,345 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 (46345 hom., cov: 32)
• Consequence: STN1 NM_024928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870
• Publications: 14 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=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.964 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STN1	NM_024928.5	c.133+2366T>C		intron_variant	Intron 2 of 9	ENST00000224950.8	NP_079204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STN1	ENST00000224950.8	c.133+2366T>C		intron_variant	Intron 2 of 9	1	NM_024928.5	ENSP00000224950.3

Frequencies

GnomAD3 genomes AF: 0.760 AC: 115530 AN: 152010 Hom.: 46340 Cov.: 32

Gnomad AFR AF: 0.478

Gnomad AMI AF: 0.950

Gnomad AMR AF: 0.851

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.899

Gnomad FIN AF: 0.881

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.781

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

GnomAD4 genome AF: 0.760 AC: 115560 AN: 152128 Hom.: 46345 Cov.: 32 AF XY: 0.766 AC XY: 57006 AN XY: 74384

African (AFR) AF: 0.478 AC: 19802 AN: 41432

American (AMR) AF: 0.851 AC: 13028 AN: 15304

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

East Asian (EAS) AF: 0.986 AC: 5111 AN: 5182

South Asian (SAS) AF: 0.901 AC: 4341 AN: 4820

European-Finnish (FIN) AF: 0.881 AC: 9335 AN: 10600

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

European-Non Finnish (NFE) AF: 0.858 AC: 58346 AN: 68000

Other (OTH) AF: 0.777 AC: 1640 AN: 2112

Alfa AF: 0.839 Hom.: 78737

Bravo AF: 0.746

Asia WGS AF: 0.870 AC: 3028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.7
DANN	Benign	0.49
PhyloP100		0.087
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: rs1265164; hg19: chr10-105674854;