Variant 1-185160846-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017673.7(SWT1):c.5C>A(p.Ser2Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000311 in 1,610,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SWT1
NM_017673.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.338

Variant links:

Genes affected

SWT1 (HGNC:16785): (SWT1 RNA endoribonuclease homolog) Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SWT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08560181).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SWT1	NM_017673.7 linkuse as main transcript	c.5C>A	p.Ser2Tyr	missense_variant	2/19	ENST00000367500.9	NP_060143.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
SWT1	ENST00000367500.9 linkuse as main transcript	c.5C>A	p.Ser2Tyr	missense_variant	2/19	1	NM_017673.7	ENSP00000356470	P1
SWT1	ENST00000367501.7 linkuse as main transcript	c.5C>A	p.Ser2Tyr	missense_variant	2/19	2		ENSP00000356471	P1
SWT1	ENST00000450350.1 linkuse as main transcript	c.5C>A	p.Ser2Tyr	missense_variant	2/5	2		ENSP00000401413

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152006

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458274

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

725312

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152006

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 08, 2023

The c.5C>A (p.S2Y) alteration is located in exon 2 (coding exon 1) of the SWT1 gene. This alteration results from a C to A substitution at nucleotide position 5, causing the serine (S) at amino acid position 2 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0025

T;T;.

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.56

.;T;T

M_CAP

Benign

0.058

MetaRNN

Benign

0.086

T;T;T

MetaSVM

Benign

-0.85

MutationAssessor

Benign

1.7

L;L;.

MutationTaster

Benign

0.56

D;D

PrimateAI

Benign

0.48

PROVEAN

Benign

-2.0

N;N;D

REVEL

Benign

0.042

Sift

Pathogenic

0.0

D;D;D

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.020

B;B;.

Vest4

0.47

MutPred

0.27

Gain of ubiquitination at K4 (P = 0.0432);Gain of ubiquitination at K4 (P = 0.0432);Gain of ubiquitination at K4 (P = 0.0432);

MVP

0.076

MPC

0.24

ClinPred

0.34

GERP RS

2.4

Varity_R

0.11

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over