NM_024928.5:c.133+755G>T

Variant names:

• chr10-103916707-C-A
• rs9420907
• NM_024928.5:c.133+755G>T

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+755G>T 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 151,708 control chromosomes in the GnomAD database, including 46,114 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 (46114 hom., cov: 29)
• Consequence: STN1 NM_024928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 104 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=-0.71).
• 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STN1	NM_024928.5	MANE Select	c.133+755G>T		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.133+755G>T		intron	N/A	ENSP00000224950.3
	STN1	ENST00000698305.1		c.133+755G>T		intron	N/A	ENSP00000513665.1
	STN1	ENST00000369764.2	TSL:2	c.133+755G>T		intron	N/A	ENSP00000358779.1

Frequencies

GnomAD3 genomes AF: 0.759 AC: 115039 AN: 151588 Hom.: 46108 Cov.: 29

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.850

Gnomad ASJ AF: 0.822

Gnomad EAS AF: 0.987

Gnomad SAS AF: 0.901

Gnomad FIN AF: 0.882

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.758 AC: 115070 AN: 151708 Hom.: 46114 Cov.: 29 AF XY: 0.765 AC XY: 56737 AN XY: 74156

African (AFR) AF: 0.472 AC: 19434 AN: 41158

American (AMR) AF: 0.850 AC: 12981 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 2853 AN: 3470

East Asian (EAS) AF: 0.986 AC: 5113 AN: 5184

South Asian (SAS) AF: 0.902 AC: 4352 AN: 4824

European-Finnish (FIN) AF: 0.882 AC: 9272 AN: 10518

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

European-Non Finnish (NFE) AF: 0.858 AC: 58337 AN: 67980

Other (OTH) AF: 0.773 AC: 1627 AN: 2104

Alfa AF: 0.820 Hom.: 119246

Bravo AF: 0.743

Asia WGS AF: 0.869 AC: 3024 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.6
DANN	Benign	0.77
PhyloP100		-1.0
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: rs9420907; hg19: chr10-105676465;