rs940389

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006873.4(STON1):c.380G>C(p.Arg127Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 1,568,372 control chromosomes in the GnomAD database, including 92,201 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.34 ( 9047 hom., cov: 32)

Exomes 𝑓: 0.34 ( 83154 hom. )

Consequence

STON1
NM_006873.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.36

Publications

32 publications found

Variant links:

Genes affected

STON1 (HGNC:17003): (stonin 1) Endocytosis of cell surface proteins is mediated by a complex molecular machinery that assembles on the inner surface of the plasma membrane. This gene encodes one of two human homologs of the Drosophila melanogaster stoned B protein. This protein is related to components of the endocytic machinery and exhibits a modular structure consisting of an N-terminal proline-rich domain, a central region of homology specific to the human stoned B-like proteins, and a C-terminal region homologous to the mu subunits of adaptor protein (AP) complexes. Read-through transcription of this gene into the neighboring downstream gene, which encodes TFIIA-alpha/beta-like factor, generates a transcript (SALF), which encodes a fusion protein comprised of sequence sharing identity with each individual gene product. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

STON1 links:

STON1-GTF2A1L (HGNC:30651): (STON1-GTF2A1L readthrough) STON1-GTF2A1L mRNAs are infrequent but naturally occurring read-through products of the neighboring STON1 and GTF2A1L genes. These transcripts encode fusion proteins composed of the vast majority of each of the individual elements, stonin 1 and general transcription factor IIA, 1-like. Alternative splicing results in multiple transcript variants. The significance of these read-through variants and the function of the resulting protein products have not yet been determined. [provided by RefSeq, Oct 2010]

STON1-GTF2A1L links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0010421574).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STON1	NM_006873.4 link	c.380G>C	p.Arg127Thr	missense_variant	Exon 2 of 4	ENST00000404752.6	NP_006864.2	Q9Y6Q2-1B2RB25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STON1	ENST00000404752.6 link	c.380G>C	p.Arg127Thr	missense_variant	Exon 2 of 4	1	NM_006873.4	ENSP00000385273.1		Q9Y6Q2-1
STON1-GTF2A1L	ENST00000394751.5 link	c.380G>C	p.Arg127Thr	missense_variant	Exon 1 of 8	2		ENSP00000378234.3		A0A0A6YYG5

Frequencies

GnomAD3 genomes

AF:

0.342

AC:

51916

AN:

151902

Hom.:

9034

Cov.:

show subpopulations

Gnomad AFR

AF:

0.320

Gnomad AMI

AF:

0.307

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.241

Gnomad EAS

AF:

0.423

Gnomad SAS

AF:

0.410

Gnomad FIN

AF:

0.451

Gnomad MID

AF:

0.248

Gnomad NFE

AF:

0.336

Gnomad OTH

AF:

0.328

GnomAD2 exomes

AF:

0.354

AC:

73319

AN:

206930

AF XY:

0.357

show subpopulations

Gnomad AFR exome

AF:

0.316

Gnomad AMR exome

AF:

0.315

Gnomad ASJ exome

AF:

0.248

Gnomad EAS exome

AF:

0.422

Gnomad FIN exome

AF:

0.458

Gnomad NFE exome

AF:

0.333

Gnomad OTH exome

AF:

0.345

GnomAD4 exome

AF:

0.339

AC:

480750

AN:

1416352

Hom.:

83154

Cov.:

AF XY:

0.342

AC XY:

239608

AN XY:

700940

show subpopulations

African (AFR)

AF:

0.315

AC:

10086

AN:

31970

American (AMR)

AF:

0.311

AC:

11399

AN:

36606

Ashkenazi Jewish (ASJ)

AF:

0.242

AC:

5542

AN:

22864

East Asian (EAS)

AF:

0.425

AC:

16693

AN:

39296

South Asian (SAS)

AF:

0.404

AC:

30943

AN:

76616

European-Finnish (FIN)

AF:

0.455

AC:

23522

AN:

51748

Middle Eastern (MID)

AF:

0.238

AC:

1317

AN:

5534

European-Non Finnish (NFE)

AF:

0.331

AC:

361603

AN:

1093250

Other (OTH)

AF:

0.336

AC:

19645

AN:

58468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

21991

43983

65974

87966

109957

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11848

23696

35544

47392

59240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.342

AC:

51978

AN:

152020

Hom.:

9047

Cov.:

AF XY:

0.348

AC XY:

25880

AN XY:

74280

show subpopulations

African (AFR)

AF:

0.320

AC:

13282

AN:

41474

American (AMR)

AF:

0.331

AC:

5050

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.241

AC:

837

AN:

3468

East Asian (EAS)

AF:

0.422

AC:

2181

AN:

5174

South Asian (SAS)

AF:

0.410

AC:

1976

AN:

4816

European-Finnish (FIN)

AF:

0.451

AC:

4760

AN:

10560

Middle Eastern (MID)

AF:

0.257

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.336

AC:

22840

AN:

67956

Other (OTH)

AF:

0.331

AC:

698

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1755

3509

5264

7018

8773

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.331

Hom.:

5359

Bravo

AF:

0.325

TwinsUK

AF:

0.343

AC:

1273

ALSPAC

AF:

0.320

AC:

1235

ESP6500AA

AF:

0.318

AC:

1400

ESP6500EA

AF:

0.332

AC:

2852

ExAC

AF:

0.348

AC:

42114

Asia WGS

AF:

0.422

AC:

1455

AN:

3454

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.3

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.0039

T;T;T;.;.;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.32

.;.;T;.;T;T;T

MetaRNN

Benign

0.0010

T;T;T;T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.0

N;N;N;.;.;.;.

PhyloP100

1.4

PrimateAI

Benign

0.27

PROVEAN

Benign

0.29

.;N;N;N;N;N;N

REVEL

Benign

0.035

Sift

Benign

0.030

.;D;D;D;D;D;D

Sift4G

Uncertain

0.012

.;D;D;D;D;D;D

Polyphen

0.039

B;B;B;B;.;B;.

Vest4

0.12, 0.11, 0.13, 0.13, 0.13, 0.13

MPC

0.0029

ClinPred

0.0026

GERP RS

2.8

PromoterAI

0.0016

Neutral

(source)

Varity_R

0.031

gMVP

0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over