rs3752949

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STN1	NM_024928.5	c.134-123T>C		intron_variant	Intron 2 of 9	ENST00000224950.8	NP_079204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STN1	ENST00000224950.8	c.134-123T>C		intron_variant	Intron 2 of 9	1	NM_024928.5	ENSP00000224950.3

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

Gnomad4 AFR exome AF: 0.208

Gnomad4 AMR exome AF: 0.204

Gnomad4 ASJ exome AF: 0.227

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.224

Gnomad4 OTH exome AF: 0.212

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

Gnomad4 AFR AF: 0.211

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.162

Gnomad4 SAS AF: 0.135

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.229

Alfa AF: 0.220 Hom.: 2194

Bravo AF: 0.221

Asia WGS AF: 0.148 AC: 514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	9.9
DANN	Benign	0.83

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