Genetic Variant STN1:p.Arg336His (chr10-103882784-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_024928.5(STN1):c.1007G>A(p.Arg336His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000134 in 1,614,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000084 ( 0 hom. )

Consequence

STN1
NM_024928.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0250

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.005407661).

BP6

Variant 10-103882784-C-T is Benign according to our data. Variant chr10-103882784-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1143264.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STN1	NM_024928.5 link	c.1007G>A	p.Arg336His	missense_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.1007G>A	p.Arg336His	missense_variant	Exon 10 of 10	1	NM_024928.5	ENSP00000224950.3		Q9H668

Frequencies

GnomAD3 genomes

AF:

0.000611

AC:

AN:

152210

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00215

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000203

AC:

AN:

251214

Hom.:

AF XY:

0.000140

AC XY:

AN XY:

135740

show subpopulations

Gnomad AFR exome

AF:

0.00277

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000352

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000841

AC:

123

AN:

1461826

Hom.:

Cov.:

AF XY:

0.0000605

AC XY:

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.00275

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000611

AC:

AN:

152328

Hom.:

Cov.:

AF XY:

0.000604

AC XY:

AN XY:

74490

show subpopulations

Gnomad4 AFR

AF:

0.00214

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000154

Hom.:

Bravo

AF:

0.000623

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000222

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 16, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.76

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.0046

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.63

.;T

M_CAP

Benign

0.0060

MetaRNN

Benign

0.0054

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.22

N;N

PrimateAI

Benign

0.22

PROVEAN

Benign

0.020

N;N

REVEL

Benign

0.023

Sift

Benign

0.23

T;T

Sift4G

Benign

0.19

T;T

Polyphen

0.0030

B;B

Vest4

0.073

MVP

0.040

MPC

0.17

ClinPred

0.010

GERP RS

-5.0

Varity_R

0.020

gMVP

0.21

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