10-103900068-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_024928.5(STN1):c.451A>G(p.Thr151Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.901 in 1,613,648 control chromosomes in the GnomAD database, including 657,760 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.85 ( 55440 hom., cov: 32)

Exomes 𝑓: 0.91 ( 602320 hom. )

Consequence

STN1
NM_024928.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.54

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 links:

ENSG00000289744 (HGNC:):

ENSG00000289744 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=6.8094437E-7).

BP6

Variant 10-103900068-T-C is Benign according to our data. Variant chr10-103900068-T-C is described in ClinVar as [Benign]. Clinvar id is 1169388.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STN1	NM_024928.5 link	c.451A>G	p.Thr151Ala	missense_variant	Exon 5 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.451A>G	p.Thr151Ala	missense_variant	Exon 5 of 10	1	NM_024928.5	ENSP00000224950.3		Q9H668

Frequencies

GnomAD3 genomes

AF:

0.847

AC:

128746

AN:

152086

Hom.:

55409

Cov.:

show subpopulations

Gnomad AFR

AF:

0.674

Gnomad AMI

AF:

0.951

Gnomad AMR

AF:

0.918

Gnomad ASJ

AF:

0.909

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.980

Gnomad FIN

AF:

0.912

Gnomad MID

AF:

0.899

Gnomad NFE

AF:

0.898

Gnomad OTH

AF:

0.868

GnomAD3 exomes

AF:

0.912

AC:

228833

AN:

251018

Hom.:

105019

AF XY:

0.917

AC XY:

124375

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.670

Gnomad AMR exome

AF:

0.946

Gnomad ASJ exome

AF:

0.908

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.981

Gnomad FIN exome

AF:

0.918

Gnomad NFE exome

AF:

0.902

Gnomad OTH exome

AF:

0.916

GnomAD4 exome

AF:

0.907

AC:

1325010

AN:

1461444

Hom.:

602320

Cov.:

AF XY:

0.909

AC XY:

660926

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.660

Gnomad4 AMR exome

AF:

0.942

Gnomad4 ASJ exome

AF:

0.912

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.981

Gnomad4 FIN exome

AF:

0.920

Gnomad4 NFE exome

AF:

0.903

Gnomad4 OTH exome

AF:

0.907

GnomAD4 genome

AF:

0.846

AC:

128823

AN:

152204

Hom.:

55440

Cov.:

AF XY:

0.851

AC XY:

63360

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.674

Gnomad4 AMR

AF:

0.919

Gnomad4 ASJ

AF:

0.909

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.982

Gnomad4 FIN

AF:

0.912

Gnomad4 NFE

AF:

0.898

Gnomad4 OTH

AF:

0.870

Alfa

AF:

0.894

Hom.:

157587

Bravo

AF:

0.839

TwinsUK

AF:

0.901

AC:

3342

ALSPAC

AF:

0.900

AC:

3470

ESP6500AA

AF:

0.678

AC:

2987

ESP6500EA

AF:

0.897

AC:

7714

ExAC

AF:

0.907

AC:

110134

Asia WGS

AF:

0.965

AC:

3356

AN:

3478

EpiCase

AF:

0.896

EpiControl

AF:

0.901

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jun 11, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 27346685) -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Cerebroretinal microangiopathy with calcifications and cysts 2

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.81

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.17

DANN

Benign

0.71

DEOGEN2

Benign

0.0075

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.010

LIST_S2

Benign

0.013

.;T

MetaRNN

Benign

6.8e-7

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.65

N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.39

N;N

REVEL

Benign

0.031

Sift

Benign

0.67

T;T

Sift4G

Benign

0.57

T;T

Polyphen

0.0

B;B

Vest4

0.012

MPC

0.13

ClinPred

0.0015

GERP RS

-3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.071

gMVP

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over