Genetic Variant NM_024928.5:c.*3201T>C (chr10-103879483-A-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.*3201T>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 0.455 in 152,476 control chromosomes in the GnomAD database, including 16,501 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 0.45 ( 16446 hom., cov: 33)

Exomes 𝑓: 0.49 ( 55 hom. )

Consequence

STN1
NM_024928.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.19

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=-0.9).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.505 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STN1	NM_024928.5	MANE Select	c.*3201T>C		3_prime_UTR	Exon 10 of 10	NP_079204.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
STN1	ENST00000224950.8	TSL:1 MANE Select	c.*3201T>C	3_prime_UTR	Exon 10 of 10	ENSP00000224950.3
STN1	ENST00000466828.6	TSL:5	n.*3757T>C	non_coding_transcript_exon	Exon 11 of 11	ENSP00000513624.1
STN1	ENST00000369764.2	TSL:2	c.*3201T>C	3_prime_UTR	Exon 9 of 9	ENSP00000358779.1

Frequencies

GnomAD3 genomes

AF:

0.455

AC:

69078

AN:

151922

Hom.:

16441

Cov.:

show subpopulations

Gnomad AFR

AF:

0.321

Gnomad AMI

AF:

0.776

Gnomad AMR

AF:

0.505

Gnomad ASJ

AF:

0.398

Gnomad EAS

AF:

0.329

Gnomad SAS

AF:

0.420

Gnomad FIN

AF:

0.622

Gnomad MID

AF:

0.465

Gnomad NFE

AF:

0.509

Gnomad OTH

AF:

0.466

GnomAD4 exome

AF:

0.493

AC:

215

AN:

436

Hom.:

Cov.:

AF XY:

0.507

AC XY:

144

AN XY:

284

show subpopulations

African (AFR)

AF:

0.438

AC:

AN:

American (AMR)

AF:

0.500

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.625

AC:

AN:

East Asian (EAS)

AF:

0.214

AC:

AN:

South Asian (SAS)

AF:

0.750

AC:

AN:

European-Finnish (FIN)

AF:

0.596

AC:

AN:

Middle Eastern (MID)

AF:

0.250

AC:

AN:

European-Non Finnish (NFE)

AF:

0.493

AC:

138

AN:

280

Other (OTH)

AF:

0.458

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.454

AC:

69098

AN:

152040

Hom.:

16446

Cov.:

AF XY:

0.459

AC XY:

34137

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.321

AC:

13289

AN:

41454

American (AMR)

AF:

0.505

AC:

7723

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.398

AC:

1383

AN:

3472

East Asian (EAS)

AF:

0.328

AC:

1694

AN:

5164

South Asian (SAS)

AF:

0.421

AC:

2032

AN:

4822

European-Finnish (FIN)

AF:

0.622

AC:

6569

AN:

10566

Middle Eastern (MID)

AF:

0.449

AC:

132

AN:

294

European-Non Finnish (NFE)

AF:

0.509

AC:

34590

AN:

67956

Other (OTH)

AF:

0.464

AC:

978

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1916

3831

5747

7662

9578

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<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:

0.490

Hom.:

10376

Bravo

AF:

0.441

Asia WGS

AF:

0.362

AC:

1261

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

5.8

(source)

DANN

Benign

0.75

PhyloP100

1.2

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over