chr10-103882797-G-T

Variant names:

• chr10-103882797-G-T
• rs758924832
• NM_024928.5:c.994C>A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_024928.5(STN1):​c.994C>A​(p.Arg332Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: STN1 NM_024928.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21

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 Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.773

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STN1	NM_024928.5	c.994C>A	p.Arg332Ser	missense_variant	Exon 10 of 10	ENST00000224950.8	NP_079204.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STN1	ENST00000224950.8	c.994C>A	p.Arg332Ser	missense_variant	Exon 10 of 10	1	NM_024928.5	ENSP00000224950.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.0000159 AC: 4 AN: 251008 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135626

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000410 AC: 6 AN: 1461748 Hom.: 0 Cov.: 30 AF XY: 0.00000550 AC XY: 4 AN XY: 727182

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.39
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.035	T;T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	.;T
M_CAP	Benign	0.059	D
MetaRNN	Pathogenic	0.77	D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Uncertain	2.6	M;M
PrimateAI	Benign	0.24	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Benign	0.22
Sift	Uncertain	0.010	D;D
Sift4G	Uncertain	0.013	D;D
Polyphen		0.85	P;P
Vest4		0.66
MutPred		0.70		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP		0.58
MPC		0.62
ClinPred		0.59	D
GERP RS		4.0
Varity_R		0.39
gMVP		0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs758924832; hg19: chr10-105642555; COSMIC: COSV56544631; COSMIC: COSV56544631;