NM_024928.5:c.-102T>G

Variant names:

• chr10-103918139-A-C
• rs4387287
• NM_024928.5:c.-102T>G

Variant summary

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

The NM_024928.5(STN1):​c.-102T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 152,622 control chromosomes in the GnomAD database, including 40,268 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 0.69 (40110 hom., cov: 33)
  • Exomes 𝑓: 0.80 (158 hom.)
• Consequence: STN1 NM_024928.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 77 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=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.826 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.-102T>G		5_prime_UTR	Exon 1 of 10	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.-102T>G		5_prime_UTR	Exon 1 of 10	ENSP00000224950.3	Q9H668
	STN1	ENST00000698305.1		c.-102T>G		5_prime_UTR	Exon 1 of 10	ENSP00000513665.1	A0A8V8TM56
	STN1	ENST00000369764.2	TSL:2	c.-545T>G		5_prime_UTR	Exon 1 of 9	ENSP00000358779.1	Q9H668

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105558 AN: 152010 Hom.: 40109 Cov.: 33

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.942

Gnomad AMR AF: 0.766

Gnomad ASJ AF: 0.797

Gnomad EAS AF: 0.825

Gnomad SAS AF: 0.808

Gnomad FIN AF: 0.861

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.719

GnomAD4 exome AF: 0.800 AC: 395 AN: 494 Hom.: 158 Cov.: 0 AF XY: 0.799 AC XY: 294 AN XY: 368

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.714 AC: 10 AN: 14

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AF: 0.750 AC: 9 AN: 12

South Asian (SAS) AF: 0.826 AC: 119 AN: 144

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 0.667 AC: 4 AN: 6

European-Non Finnish (NFE) AF: 0.804 AC: 246 AN: 306

Other (OTH) AF: 0.500 AC: 3 AN: 6

GnomAD4 genome AF: 0.694 AC: 105567 AN: 152128 Hom.: 40110 Cov.: 33 AF XY: 0.699 AC XY: 52014 AN XY: 74376

African (AFR) AF: 0.353 AC: 14655 AN: 41470

American (AMR) AF: 0.766 AC: 11721 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.797 AC: 2765 AN: 3468

East Asian (EAS) AF: 0.825 AC: 4254 AN: 5158

South Asian (SAS) AF: 0.809 AC: 3903 AN: 4826

European-Finnish (FIN) AF: 0.861 AC: 9130 AN: 10606

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.832 AC: 56548 AN: 67984

Other (OTH) AF: 0.714 AC: 1509 AN: 2114

Alfa AF: 0.806 Hom.: 100603

Bravo AF: 0.673

Asia WGS AF: 0.750 AC: 2609 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.4
DANN	Benign	0.49
PhyloP100		0.61
PromoterAI		0.081	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs4387287; hg19: chr10-105677897;