10-103900068-T-C

Position:

• chr10-103900068-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.85 (55440 hom., cov: 32)
  • Exomes 𝑓: 0.91 (602320 hom.)
• Consequence: STN1 NM_024928.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -1.54

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]

ENSG00000289744 (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
STN1	NM_024928.5	c.451A>G	p.Thr151Ala	missense_variant	5/10	ENST00000224950.8	NP_079204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STN1	ENST00000224950.8	c.451A>G	p.Thr151Ala	missense_variant	5/10	1	NM_024928.5	ENSP00000224950.3

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128746 AN: 152086 Hom.: 55409 Cov.: 32

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

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.: 42 AF XY: 0.909 AC XY: 660926 AN XY: 727024

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.: 32 AF XY: 0.851 AC XY: 63360 AN XY: 74414

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

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 11, 2019	This variant is associated with the following publications: (PMID: 27346685) -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

Cerebroretinal microangiopathy with calcifications and cysts 2 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_addAF	Benign	-0.81	T
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	N
LIST_S2	Benign	0.013	.;T
MetaRNN	Benign	6.8e-7	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.65	N;N
PrimateAI	Benign	0.24	T
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	T
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

Other links and lift over

dbSNP: rs2487999; hg19: chr10-105659826;