Variant chr3-113567578-C-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_017699.3(SIDT1):c.383C>T(p.Thr128Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,792 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: not found (cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

SIDT1
NM_017699.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.75

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:

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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, 0.83

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIDT1	NM_017699.3 link	c.383C>T	p.Thr128Ile	missense_variant	3/25	ENST00000264852.9	NP_060169.2	Q9NXL6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SIDT1	ENST00000264852.9 link	c.383C>T	p.Thr128Ile	missense_variant	3/25	2	NM_017699.3	ENSP00000264852.4	Q9NXL6-1
SIDT1	ENST00000393830.4 link	c.383C>T	p.Thr128Ile	missense_variant	3/26	1		ENSP00000377416.4	Q9NXL6-2
SIDT1	ENST00000483946.1 link	n.228C>T		non_coding_transcript_exon_variant	3/3	4
SIDT1	ENST00000491730.5 link	n.850C>T		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251264

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135784

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461792

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727202

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:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

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

Jul 10, 2024

The c.383C>T (p.T128I) alteration is located in exon 3 (coding exon 3) of the SIDT1 gene. This alteration results from a C to T substitution at nucleotide position 383, causing the threonine (T) at amino acid position 128 to be replaced by an isoleucine (I). 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

Uncertain

0.55

BayesDel_addAF

Uncertain

0.13

BayesDel_noAF

Uncertain

0.050

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;.

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.83

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.5

M;M

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-4.0

D;D

REVEL

Benign

0.29

Sift

Benign

0.13

T;T

Sift4G

Benign

0.11

T;T

Polyphen

1.0

D;.

Vest4

0.99

MutPred

0.48

Loss of disorder (P = 0.0367);Loss of disorder (P = 0.0367);

MVP

0.11

MPC

0.48

ClinPred

0.87

GERP RS

6.2

Varity_R

0.20

gMVP

0.75

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