chr10-103910745-A-G

Variant names:

• chr10-103910745-A-G
• rs3752949
• NM_024928.5:c.134-123T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024928.5(STN1):​c.134-123T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 574,520 control chromosomes in the GnomAD database, including 13,318 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (3729 hom., cov: 32)
  • Exomes 𝑓: 0.21 (9589 hom.)
• Consequence: STN1 NM_024928.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.944
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.223 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STN1	NM_024928.5	MANE Select	c.134-123T>C		intron	N/A	NP_079204.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STN1	ENST00000224950.8	TSL:1 MANE Select	c.134-123T>C		intron	N/A	ENSP00000224950.3
	STN1	ENST00000698305.1		c.134-123T>C		intron	N/A	ENSP00000513665.1
	STN1	ENST00000369764.2	TSL:2	c.134-123T>C		intron	N/A	ENSP00000358779.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33164 AN: 152092 Hom.: 3724 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.382

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.230

GnomAD4 exome AF: 0.206 AC: 87099 AN: 422310 Hom.: 9589 AF XY: 0.202 AC XY: 45338 AN XY: 224648

African (AFR) AF: 0.208 AC: 2460 AN: 11812

American (AMR) AF: 0.204 AC: 4215 AN: 20638

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 2999 AN: 13208

East Asian (EAS) AF: 0.157 AC: 4481 AN: 28618

South Asian (SAS) AF: 0.121 AC: 5331 AN: 43996

European-Finnish (FIN) AF: 0.214 AC: 5887 AN: 27526

Middle Eastern (MID) AF: 0.213 AC: 382 AN: 1796

European-Non Finnish (NFE) AF: 0.224 AC: 56318 AN: 251004

Other (OTH) AF: 0.212 AC: 5026 AN: 23712

GnomAD4 genome AF: 0.218 AC: 33175 AN: 152210 Hom.: 3729 Cov.: 32 AF XY: 0.218 AC XY: 16191 AN XY: 74418

African (AFR) AF: 0.211 AC: 8749 AN: 41516

American (AMR) AF: 0.229 AC: 3505 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.226 AC: 785 AN: 3470

East Asian (EAS) AF: 0.162 AC: 840 AN: 5174

South Asian (SAS) AF: 0.135 AC: 651 AN: 4830

European-Finnish (FIN) AF: 0.230 AC: 2433 AN: 10590

Middle Eastern (MID) AF: 0.224 AC: 66 AN: 294

European-Non Finnish (NFE) AF: 0.225 AC: 15314 AN: 68012

Other (OTH) AF: 0.229 AC: 484 AN: 2116

Alfa AF: 0.221 Hom.: 2407

Bravo AF: 0.221

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.9
DANN	Benign	0.83
PhyloP100		0.94
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3752949; hg19: chr10-105670503; COSMIC: COSV56544863;