Genetic Variant STN1:p.Ser248Phe (chr10-103897558-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_024928.5(STN1):c.743C>T(p.Ser248Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S248C) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STN1
NM_024928.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.267

Publications

49 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.09816122).

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.743C>T	p.Ser248Phe	missense	Exon 7 of 10	NP_079204.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
STN1	ENST00000224950.8	TSL:1 MANE Select	c.743C>T	p.Ser248Phe	missense	Exon 7 of 10	ENSP00000224950.3
STN1	ENST00000698305.1		c.743C>T	p.Ser248Phe	missense	Exon 7 of 10	ENSP00000513665.1
STN1	ENST00000369764.2	TSL:2	c.743C>T	p.Ser248Phe	missense	Exon 6 of 9	ENSP00000358779.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.84e-7

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727170

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111924

Other (OTH)

AF:

0.00

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

5.1

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.017

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.081

LIST_S2

Benign

0.16

M_CAP

Benign

0.023

MetaRNN

Benign

0.098

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

PhyloP100

-0.27

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.6

REVEL

Benign

0.033

Sift

Benign

0.090

Sift4G

Uncertain

0.053

Polyphen

0.11

Vest4

0.27

MutPred

0.33

Loss of disorder (P = 0.0048)

MVP

0.048

MPC

0.24

ClinPred

0.085

GERP RS

1.4

Varity_R

0.048

gMVP

0.17

Mutation Taster

=100/0

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over