Variant chr3-113533032-G-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_017699.3(SIDT1):c.11G>A(p.Cys4Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000342 in 1,375,940 control chromosomes in the GnomAD database, including 1 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 1 hom. )

Consequence

SIDT1
NM_017699.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0320

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 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=0.090575606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIDT1	NM_017699.3 linkuse as main transcript	c.11G>A	p.Cys4Tyr	missense_variant	1/25	ENST00000264852.9	NP_060169.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIDT1	ENST00000264852.9 linkuse as main transcript	c.11G>A	p.Cys4Tyr	missense_variant	1/25	2	NM_017699.3	ENSP00000264852	P4	Q9NXL6-1
SIDT1	ENST00000393830.4 linkuse as main transcript	c.11G>A	p.Cys4Tyr	missense_variant	1/26	1		ENSP00000377416	A2	Q9NXL6-2
SIDT1	ENST00000491730.5 linkuse as main transcript	n.478G>A		non_coding_transcript_exon_variant	1/6	5

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152094

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000368

AC:

AN:

1223846

Hom.:

Cov.:

AF XY:

0.0000286

AC XY:

AN XY:

594720

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:

0.0000440

Gnomad4 OTH exome

AF:

0.0000200

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152094

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74294

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

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

Jul 13, 2021

The c.11G>A (p.C4Y) alteration is located in exon 1 (coding exon 1) of the SIDT1 gene. This alteration results from a G to A substitution at nucleotide position 11, causing the cysteine (C) at amino acid position 4 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

0.088

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-0.79

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.091

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.95

N;N

REVEL

Benign

0.059

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.58

T;T

Polyphen

0.0

B;.

Vest4

0.096

MutPred

0.53

Loss of disorder (P = 0.0292);Loss of disorder (P = 0.0292);

MVP

0.11

MPC

0.28

ClinPred

0.49

GERP RS

2.4

Varity_R

0.60

gMVP

0.51

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

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