Variant chr2-48591794-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_006873.4(STON1):c.2072G>T(p.Gly691Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

STON1
NM_006873.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 7.49

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:):

STON1-GTF2A1L links:

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ACMG classification

Classification made for transcript

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, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STON1	NM_006873.4 linkuse as main transcript	c.2072G>T	p.Gly691Val	missense_variant	3/4	ENST00000404752.6
STON1-GTF2A1L	NM_001198593.2 linkuse as main transcript	c.2072G>T	p.Gly691Val	missense_variant	3/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STON1	ENST00000404752.6 linkuse as main transcript	c.2072G>T	p.Gly691Val	missense_variant	3/4	1	NM_006873.4	P1	Q9Y6Q2-1
STON1	ENST00000406226.1 linkuse as main transcript	c.2072G>T	p.Gly691Val	missense_variant	4/5	1		P1	Q9Y6Q2-1
STON1	ENST00000649748.1 linkuse as main transcript	c.2072G>T	p.Gly691Val	missense_variant	4/5			P1	Q9Y6Q2-1
STON1	ENST00000444932.1 linkuse as main transcript	c.*36G>T		3_prime_UTR_variant, NMD_transcript_variant	2/3	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Myoepithelial tumor

Uncertain:1

Uncertain significance, no assertion criteria provided

research

Caryl and Israel Englander Institute for Precision Medicine, Weill Cornell Medicine

Nov 01, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.79

BayesDel_addAF

Pathogenic

0.21

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.035

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

Eigen

Pathogenic

0.76

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.91

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

M_CAP

Benign

0.031

MetaRNN

Pathogenic

0.75

D;D;D;D;D;D;D

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.9

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

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.5

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

REVEL

Uncertain

0.32

Sift

Uncertain

0.0040

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

Sift4G

Uncertain

0.011

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

Polyphen

1.0

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

Vest4

0.81, 0.81, 0.87, 0.88, 0.87, 0.83

MutPred

0.40

Loss of disorder (P = 0.0606);Loss of disorder (P = 0.0606);Loss of disorder (P = 0.0606);Loss of disorder (P = 0.0606);Loss of disorder (P = 0.0606);Loss of disorder (P = 0.0606);Loss of disorder (P = 0.0606);

MVP

0.70

MPC

0.012

ClinPred

0.99

GERP RS

4.6

Varity_R

0.69

gMVP

0.56

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over