10-103879756-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024928.5(STN1):c.*2928A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.331 in 153,148 control chromosomes in the GnomAD database, including 9,104 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 0.33 (9005 hom., cov: 34)
  • Exomes 𝑓: 0.43 (99 hom.)
• Consequence: STN1 NM_024928.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.693

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.409 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STN1	NM_024928.5	c.*2928A>C		3_prime_UTR_variant	10/10	ENST00000224950.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STN1	ENST00000224950.8	c.*2928A>C		3_prime_UTR_variant	10/10	1	NM_024928.5	P1

Frequencies

GnomAD3 genomes AF: 0.330 AC: 50229 AN: 152022 Hom.: 9006 Cov.: 34

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.449

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.329

GnomAD4 exome AF: 0.428 AC: 431 AN: 1008 Hom.: 99 Cov.: 0 AF XY: 0.434 AC XY: 335 AN XY: 772

Gnomad4 AFR exome AF: 0.125

Gnomad4 AMR exome AF: 0.500

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.154

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.444

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.330 AC: 50246 AN: 152140 Hom.: 9005 Cov.: 34 AF XY: 0.327 AC XY: 24318 AN XY: 74368

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.449

Gnomad4 EAS AF: 0.279

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.413

Gnomad4 OTH AF: 0.325

Alfa AF: 0.384 Hom.: 15086

Bravo AF: 0.322

Asia WGS AF: 0.330 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.8
Dann	Benign	0.76

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10748858; hg19: chr10-105639514;