Variant 3-113584728-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_017699.3(SIDT1):c.866G>A(p.Arg289Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00005 in 1,599,364 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 (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

SIDT1
NM_017699.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.17

Variant links:

Genes affected

SIDT1 (HGNC:25967): (SID1 transmembrane family member 1) The protein encoded by this gene belongs to SID1 family of transmembrane dsRNA-gated channels. Family members transport dsRNA into cells and are required for systemic RNA interference. [provided by RefSeq, May 2017]

SIDT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIDT1	NM_017699.3 link	c.866G>A	p.Arg289Gln	missense_variant	8/25	ENST00000264852.9	NP_060169.2	Q9NXL6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SIDT1	ENST00000264852.9 link	c.866G>A	p.Arg289Gln	missense_variant	8/25	2	NM_017699.3	ENSP00000264852.4	Q9NXL6-1
SIDT1	ENST00000393830.4 link	c.866G>A	p.Arg289Gln	missense_variant	8/26	1		ENSP00000377416.4	Q9NXL6-2
SIDT1	ENST00000488390.1 link	n.47G>A		non_coding_transcript_exon_variant	1/4	4

Frequencies

GnomAD3 genomes

AF:

0.0000527

AC:

AN:

151912

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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:

0.0000294

Gnomad OTH

AF:

0.000959

GnomAD3 exomes

AF:

0.0000253

AC:

AN:

237250

Hom.:

AF XY:

0.0000234

AC XY:

AN XY:

128086

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000370

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000456

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000497

AC:

AN:

1447452

Hom.:

Cov.:

AF XY:

0.0000528

AC XY:

AN XY:

719670

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000490

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000254

Gnomad4 SAS exome

AF:

0.0000242

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000569

Gnomad4 OTH exome

AF:

0.0000502

GnomAD4 genome

AF:

0.0000527

AC:

AN:

151912

Hom.:

Cov.:

AF XY:

0.0000674

AC XY:

AN XY:

74166

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.0000656

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000959

Alfa

AF:

0.0000901

Hom.:

Bravo

AF:

0.0000680

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.0000330

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Feb 15, 2023

The c.866G>A (p.R289Q) alteration is located in exon 8 (coding exon 8) of the SIDT1 gene. This alteration results from a G to A substitution at nucleotide position 866, causing the arginine (R) at amino acid position 289 to be replaced by a glutamine (Q). 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

0.13

BayesDel_addAF

Uncertain

0.045

BayesDel_noAF

Uncertain

0.010

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.17

T;.

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.59

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.92

D;D

M_CAP

Benign

0.017

MetaRNN

Pathogenic

0.95

D;D

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-2.6

D;D

REVEL

Uncertain

0.35

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0050

D;D

Polyphen

1.0

D;D

Vest4

0.65

MutPred

0.81

Gain of ubiquitination at K290 (P = 0.0354);Gain of ubiquitination at K290 (P = 0.0354);

MVP

0.47

MPC

0.25

ClinPred

0.52

GERP RS

6.0

Varity_R

0.32

gMVP

0.71

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