Genetic Variant STN1:c.*2928A>C (chr10-103879756-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024928.5(STN1):c.*2928A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 153,148 control chromosomes in the GnomAD database, including 9,104 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 0.33 ( 9005 hom., cov: 34)

Exomes 𝑓: 0.43 ( 99 hom. )

Consequence

STN1
NM_024928.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.693

Publications

20 publications found

Variant links:

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

STN1 links:

ENSG00000289744 (HGNC:):

ENSG00000289744 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STN1	NM_024928.5 link	c.*2928A>C		3_prime_UTR_variant	Exon 10 of 10	ENST00000224950.8	NP_079204.2	Q9H668

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STN1	ENST00000224950.8 link	c.*2928A>C		3_prime_UTR_variant	Exon 10 of 10	1	NM_024928.5	ENSP00000224950.3		Q9H668

Frequencies

GnomAD3 genomes

AF:

0.330

AC:

50229

AN:

152022

Hom.:

9006

Cov.:

show subpopulations

Gnomad AFR

AF:

0.185

Gnomad AMI

AF:

0.208

Gnomad AMR

AF:

0.331

Gnomad ASJ

AF:

0.449

Gnomad EAS

AF:

0.278

Gnomad SAS

AF:

0.413

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.389

Gnomad NFE

AF:

0.413

Gnomad OTH

AF:

0.329

GnomAD4 exome

AF:

0.428

AC:

431

AN:

1008

Hom.:

Cov.:

AF XY:

0.434

AC XY:

335

AN XY:

772

show subpopulations

African (AFR)

AF:

0.125

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

AN:

East Asian (EAS)

AF:

0.154

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.444

AC:

341

AN:

768

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.330

AC:

50246

AN:

152140

Hom.:

9005

Cov.:

AF XY:

0.327

AC XY:

24318

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.185

AC:

7695

AN:

41498

American (AMR)

AF:

0.331

AC:

5059

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.449

AC:

1556

AN:

3468

East Asian (EAS)

AF:

0.279

AC:

1442

AN:

5174

South Asian (SAS)

AF:

0.413

AC:

1995

AN:

4828

European-Finnish (FIN)

AF:

0.327

AC:

3459

AN:

10592

Middle Eastern (MID)

AF:

0.398

AC:

117

AN:

294

European-Non Finnish (NFE)

AF:

0.413

AC:

28048

AN:

67976

Other (OTH)

AF:

0.325

AC:

685

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1715

3430

5145

6860

8575

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

506

1012

1518

2024

2530

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.379

Hom.:

20288

Bravo

AF:

0.322

Asia WGS

AF:

0.330

AC:

1149

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

1.8

(source)

DANN

Benign

0.76

PhyloP100

0.69

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over