10-103897558-G-C

Variant names:

• chr10-103897558-G-C
• rs10786775
• NM_024928.5:c.743C>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024928.5(STN1):​c.743C>G​(p.Ser248Cys) 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 1,613,708 control chromosomes in the GnomAD database, including 657,846 homozygotes. 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 Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.85 (55458 hom., cov: 32)
  • Exomes 𝑓: 0.91 (602388 hom.)
• Consequence: STN1 NM_024928.5 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.267
• Publications: 49 publications found

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

ENSG00000289744 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=1.4304446E-6).
• BP6: Variant 10-103897558-G-C is Benign according to our data. Variant chr10-103897558-G-C is described in ClinVar as Benign. ClinVar VariationId is 1169155.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.

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>G	p.Ser248Cys	missense	Exon 7 of 10	NP_079204.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STN1	ENST00000224950.8	TSL:1 MANE Select	c.743C>G	p.Ser248Cys	missense	Exon 7 of 10	ENSP00000224950.3
	STN1	ENST00000698305.1		c.743C>G	p.Ser248Cys	missense	Exon 7 of 10	ENSP00000513665.1
	STN1	ENST00000369764.2	TSL:2	c.743C>G	p.Ser248Cys	missense	Exon 6 of 9	ENSP00000358779.1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128777 AN: 152104 Hom.: 55427 Cov.: 32

Gnomad AFR AF: 0.675

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

GnomAD2 exomes AF: 0.912 AC: 228915 AN: 251122 AF XY: 0.917

Gnomad AFR exome AF: 0.669

Gnomad AMR exome AF: 0.946

Gnomad ASJ exome AF: 0.908

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.918

Gnomad NFE exome AF: 0.902

Gnomad OTH exome AF: 0.916

GnomAD4 exome AF: 0.907 AC: 1325101 AN: 1461486 Hom.: 602388 Cov.: 42 AF XY: 0.909 AC XY: 660971 AN XY: 727038

African (AFR) AF: 0.660 AC: 22081 AN: 33458

American (AMR) AF: 0.942 AC: 42118 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.912 AC: 23825 AN: 26126

East Asian (EAS) AF: 1.00 AC: 39697 AN: 39700

South Asian (SAS) AF: 0.981 AC: 84588 AN: 86256

European-Finnish (FIN) AF: 0.920 AC: 49115 AN: 53414

Middle Eastern (MID) AF: 0.904 AC: 5184 AN: 5734

European-Non Finnish (NFE) AF: 0.903 AC: 1003745 AN: 1111710

Other (OTH) AF: 0.907 AC: 54748 AN: 60370

GnomAD4 genome AF: 0.846 AC: 128854 AN: 152222 Hom.: 55458 Cov.: 32 AF XY: 0.851 AC XY: 63369 AN XY: 74422

African (AFR) AF: 0.674 AC: 27971 AN: 41486

American (AMR) AF: 0.919 AC: 14052 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.909 AC: 3156 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5183 AN: 5184

South Asian (SAS) AF: 0.981 AC: 4744 AN: 4834

European-Finnish (FIN) AF: 0.912 AC: 9672 AN: 10606

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.898 AC: 61105 AN: 68024

Other (OTH) AF: 0.870 AC: 1840 AN: 2116

Alfa AF: 0.888 Hom.: 19107

Bravo AF: 0.839

TwinsUK AF: 0.901 AC: 3342

ALSPAC AF: 0.900 AC: 3468

ESP6500AA AF: 0.678 AC: 2987

ESP6500EA AF: 0.897 AC: 7715

ExAC AF: 0.907 AC: 110126

Asia WGS AF: 0.964 AC: 3351 AN: 3478

EpiCase AF: 0.896

EpiControl AF: 0.901

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.045
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.4
DANN	Benign	0.31
DEOGEN2	Benign	0.0034	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0034	N
LIST_S2	Benign	0.070	T
MetaRNN	Benign	0.0000014	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.1	N
PhyloP100		-0.27
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.86	N
REVEL	Benign	0.052
Sift	Benign	0.24	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.042
MPC		0.13
ClinPred		0.0017	T
GERP RS		1.4
Varity_R		0.031
gMVP		0.14
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10786775; hg19: chr10-105657316; COSMIC: COSV108081681;