2-48580986-G-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_006873.4(STON1):c.353G>T(p.Gly118Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00485 in 1,575,930 control chromosomes in the GnomAD database, including 72 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0040 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0049 ( 67 hom. )

Consequence

STON1
NM_006873.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.279

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004071653).

BP6

Variant 2-48580986-G-T is Benign according to our data. Variant chr2-48580986-G-T is described in ClinVar as [Benign]. Clinvar id is 722414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00399 (607/152318) while in subpopulation SAS AF = 0.0297 (143/4822). AF 95% confidence interval is 0.0257. There are 5 homozygotes in GnomAd4. There are 329 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STON1	NM_006873.4 link	c.353G>T	p.Gly118Val	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.353G>T	p.Gly118Val	missense_variant	Exon 2 of 4	1	NM_006873.4	ENSP00000385273.1		Q9Y6Q2-1
STON1-GTF2A1L	ENST00000394754.5 link	c.353G>T	p.Gly118Val	missense_variant	Exon 2 of 11	1		ENSP00000378236.1		Q53S48

Frequencies

GnomAD3 genomes

AF:

0.00398

AC:

605

AN:

152200

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000917

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00403

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0296

Gnomad FIN

AF:

0.000282

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00436

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00550

AC:

1169

AN:

212648

AF XY:

0.00657

show subpopulations

Gnomad AFR exome

AF:

0.000887

Gnomad AMR exome

AF:

0.00194

Gnomad ASJ exome

AF:

0.00295

Gnomad EAS exome

AF:

0.000171

Gnomad FIN exome

AF:

0.000358

Gnomad NFE exome

AF:

0.00437

Gnomad OTH exome

AF:

0.00582

GnomAD4 exome

AF:

0.00494

AC:

7039

AN:

1423612

Hom.:

Cov.:

AF XY:

0.00555

AC XY:

3910

AN XY:

705104

show subpopulations

African (AFR)

AF:

0.000837

AC:

AN:

32240

American (AMR)

AF:

0.00215

AC:

AN:

38174

Ashkenazi Jewish (ASJ)

AF:

0.00218

AC:

AN:

23370

East Asian (EAS)

AF:

0.0000762

AC:

AN:

39360

South Asian (SAS)

AF:

0.0274

AC:

2140

AN:

77976

European-Finnish (FIN)

AF:

0.000558

AC:

AN:

52000

Middle Eastern (MID)

AF:

0.0149

AC:

AN:

5580

European-Non Finnish (NFE)

AF:

0.00391

AC:

4288

AN:

1096140

Other (OTH)

AF:

0.00572

AC:

336

AN:

58772

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

397

794

1190

1587

1984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00399

AC:

607

AN:

152318

Hom.:

Cov.:

AF XY:

0.00442

AC XY:

329

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000914

AC:

AN:

41572

American (AMR)

AF:

0.00576

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00403

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.0297

AC:

143

AN:

4822

European-Finnish (FIN)

AF:

0.000282

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00438

AC:

298

AN:

68040

Other (OTH)

AF:

0.0104

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

125

156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00423

Hom.:

Bravo

AF:

0.00340

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00588

AC:

713

Asia WGS

AF:

0.00960

AC:

AN:

3448

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 13, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

1.5

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.075

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

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.28

LIST_S2

Benign

0.72

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

MetaRNN

Benign

0.0041

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

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;M;M;.;.;.;.

PhyloP100

0.28

PrimateAI

Benign

0.27

PROVEAN

Benign

-2.1

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

REVEL

Benign

0.030

Sift

Uncertain

0.0020

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

Sift4G

Uncertain

0.019

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

Polyphen

0.68

P;P;P;P;.;P;.

Vest4

0.28, 0.28, 0.27, 0.23

MVP

0.46

MPC

0.0064

ClinPred

0.023

GERP RS

1.9

PromoterAI

-0.0067

Neutral

(source)

Varity_R

0.057

gMVP

0.32

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

2-48580986-G-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over