chr10-103911374-A-G

Variant names:

• chr10-103911374-A-G
• rs2488001
• NM_024928.5:c.134-752T>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.134-752T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.846 in 152,016 control chromosomes in the GnomAD database, including 55,342 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 0.85 (55342 hom., cov: 30)
• Consequence: STN1 NM_024928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.479
• 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=-0.88).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STN1	NM_024928.5	MANE Select	c.134-752T>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.134-752T>C		intron	N/A	ENSP00000224950.3	Q9H668
	STN1	ENST00000698305.1		c.134-752T>C		intron	N/A	ENSP00000513665.1	A0A8V8TM56
	STN1	ENST00000369764.2	TSL:2	c.134-752T>C		intron	N/A	ENSP00000358779.1	Q9H668

Frequencies

GnomAD3 genomes AF: 0.846 AC: 128534 AN: 151898 Hom.: 55311 Cov.: 30

Gnomad AFR AF: 0.673

Gnomad AMI AF: 0.951

Gnomad AMR AF: 0.918

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.980

Gnomad FIN AF: 0.912

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.898

Gnomad OTH AF: 0.868

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

GnomAD4 genome AF: 0.846 AC: 128611 AN: 152016 Hom.: 55342 Cov.: 30 AF XY: 0.851 AC XY: 63221 AN XY: 74286

African (AFR) AF: 0.672 AC: 27829 AN: 41386

American (AMR) AF: 0.919 AC: 14045 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3154 AN: 3466

East Asian (EAS) AF: 1.00 AC: 5157 AN: 5158

South Asian (SAS) AF: 0.981 AC: 4734 AN: 4824

European-Finnish (FIN) AF: 0.912 AC: 9657 AN: 10590

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.898 AC: 61063 AN: 67982

Other (OTH) AF: 0.870 AC: 1841 AN: 2116

Alfa AF: 0.870 Hom.: 6800

Bravo AF: 0.838

Asia WGS AF: 0.964 AC: 3353 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.29
PhyloP100		-0.48
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: rs2488001; hg19: chr10-105671132;