Variant 11-117182750-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001040455.2(SIDT2):c.646G>A(p.Val216Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000684 in 1,461,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SIDT2
NM_001040455.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.53

Variant links:

Genes affected

SIDT2 (HGNC:24272): (SID1 transmembrane family member 2) Predicted to enable several functions, including AP-1 adaptor complex binding activity; AP-2 adaptor complex binding activity; and RNA transmembrane transporter activity. Involved in RNA transport. Located in lysosomal membrane and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SIDT2 links:

SIDT2 (HGNC:):

SIDT2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41513556).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIDT2	NM_001040455.2 linkuse as main transcript	c.646G>A	p.Val216Ile	missense_variant	6/26	ENST00000324225.9	NP_001035545.1	Q8NBJ9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIDT2	ENST00000324225.9 linkuse as main transcript	c.646G>A	p.Val216Ile	missense_variant	6/26	1	NM_001040455.2	ENSP00000314023.4		Q8NBJ9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000159

AC:

AN:

251224

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135790

show subpopulations

Gnomad AFR exome

AF:

0.0000616

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461826

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000113

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

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

May 09, 2023

The c.646G>A (p.V216I) alteration is located in exon 6 (coding exon 6) of the SIDT2 gene. This alteration results from a G to A substitution at nucleotide position 646, causing the valine (V) at amino acid position 216 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

Benign

0.23

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.29

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0072

T;T;T;T;T;.

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

.;D;.;D;D;D

M_CAP

Benign

0.011

MetaRNN

Benign

0.42

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;.;.;.;.

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.41

N;.;N;.;N;N

REVEL

Benign

0.28

Sift

Benign

0.35

T;.;T;.;T;T

Sift4G

Benign

0.46

T;T;T;T;T;D

Polyphen

0.99

D;D;D;D;D;.

Vest4

0.74

MutPred

0.63

Loss of catalytic residue at V216 (P = 0.041);Loss of catalytic residue at V216 (P = 0.041);Loss of catalytic residue at V216 (P = 0.041);Loss of catalytic residue at V216 (P = 0.041);Loss of catalytic residue at V216 (P = 0.041);.;

MVP

0.24

MPC

1.3

ClinPred

0.57

GERP RS

4.8

Varity_R

0.079

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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