NM_024928.5:c.949+1530T>C

Variant names:

• chr10-103887542-A-G
• rs3814220
• NM_024928.5:c.949+1530T>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.949+1530T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,942 control chromosomes in the GnomAD database, including 15,738 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 (15738 hom., cov: 31)
• Consequence: STN1 NM_024928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.738
• Publications: 8 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 (AMR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STN1	NM_024928.5	c.949+1530T>C		intron_variant	Intron 9 of 9	ENST00000224950.8	NP_079204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STN1	ENST00000224950.8	c.949+1530T>C		intron_variant	Intron 9 of 9	1	NM_024928.5	ENSP00000224950.3

Frequencies

GnomAD3 genomes AF: 0.445 AC: 67571 AN: 151822 Hom.: 15732 Cov.: 31

Gnomad AFR AF: 0.315

Gnomad AMI AF: 0.776

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.401

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.497

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.445 AC: 67588 AN: 151942 Hom.: 15738 Cov.: 31 AF XY: 0.449 AC XY: 33339 AN XY: 74268

African (AFR) AF: 0.315 AC: 13024 AN: 41404

American (AMR) AF: 0.497 AC: 7596 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.396 AC: 1373 AN: 3464

East Asian (EAS) AF: 0.343 AC: 1774 AN: 5170

South Asian (SAS) AF: 0.403 AC: 1939 AN: 4816

European-Finnish (FIN) AF: 0.599 AC: 6329 AN: 10564

Middle Eastern (MID) AF: 0.428 AC: 125 AN: 292

European-Non Finnish (NFE) AF: 0.497 AC: 33757 AN: 67930

Other (OTH) AF: 0.456 AC: 963 AN: 2110

Alfa AF: 0.461 Hom.: 2170

Bravo AF: 0.433

Asia WGS AF: 0.367 AC: 1280 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	0.92
DANN	Benign	0.26
PhyloP100		-0.74
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: rs3814220; hg19: chr10-105647300;