Genetic Variant NM_024928.5:c.*3021C>T (chr10-103879663-G-A) – 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.*3021C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,682 control chromosomes in the GnomAD database, including 45,802 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 ( 45603 hom., cov: 33)

Exomes 𝑓: 0.86 ( 199 hom. )

Consequence

STN1
NM_024928.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.63

Publications

10 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=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.958 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STN1	NM_024928.5 link	c.*3021C>T		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.*3021C>T		3_prime_UTR_variant	Exon 10 of 10	1	NM_024928.5	ENSP00000224950.3		Q9H668

Frequencies

GnomAD3 genomes

AF:

0.757

AC:

115046

AN:

152030

Hom.:

45603

Cov.:

show subpopulations

Gnomad AFR

AF:

0.495

Gnomad AMI

AF:

0.950

Gnomad AMR

AF:

0.841

Gnomad ASJ

AF:

0.821

Gnomad EAS

AF:

0.981

Gnomad SAS

AF:

0.887

Gnomad FIN

AF:

0.858

Gnomad MID

AF:

0.783

Gnomad NFE

AF:

0.848

Gnomad OTH

AF:

0.774

GnomAD4 exome

AF:

0.861

AC:

458

AN:

532

Hom.:

199

Cov.:

AF XY:

0.868

AC XY:

335

AN XY:

386

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

1.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.750

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

1.00

AC:

AN:

European-Finnish (FIN)

AF:

0.906

AC:

AN:

Middle Eastern (MID)

AF:

0.833

AC:

AN:

European-Non Finnish (NFE)

AF:

0.853

AC:

360

AN:

422

Other (OTH)

AF:

0.833

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:

0.756

AC:

115071

AN:

152150

Hom.:

45603

Cov.:

AF XY:

0.763

AC XY:

56720

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.495

AC:

20516

AN:

41470

American (AMR)

AF:

0.841

AC:

12862

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.821

AC:

2849

AN:

3472

East Asian (EAS)

AF:

0.980

AC:

5061

AN:

5162

South Asian (SAS)

AF:

0.889

AC:

4290

AN:

4828

European-Finnish (FIN)

AF:

0.858

AC:

9089

AN:

10596

Middle Eastern (MID)

AF:

0.786

AC:

231

AN:

294

European-Non Finnish (NFE)

AF:

0.848

AC:

57680

AN:

68008

Other (OTH)

AF:

0.770

AC:

1627

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1255

2511

3766

5022

6277

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

844

1688

2532

3376

4220

<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:

0.821

Hom.:

83663

Bravo

AF:

0.744

Asia WGS

AF:

0.854

AC:

2972

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.52

(source)

DANN

Benign

0.57

PhyloP100

-2.6

Splicing

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

Publications

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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