Variant 11-117181958-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001040455.2(SIDT2):c.457G>A(p.Asp153Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000574 in 1,614,174 control chromosomes in the GnomAD database, including 5 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 0.00053 ( 1 hom., cov: 31)

Exomes 𝑓: 0.00058 ( 4 hom. )

Consequence

SIDT2
NM_001040455.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007419616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIDT2	NM_001040455.2 linkuse as main transcript	c.457G>A	p.Asp153Asn	missense_variant	3/26	ENST00000324225.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIDT2	ENST00000324225.9 linkuse as main transcript	c.457G>A	p.Asp153Asn	missense_variant	3/26	1	NM_001040455.2	P3	Q8NBJ9-1

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152172

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000523

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000830

Gnomad FIN

AF:

0.00160

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000647

Gnomad OTH

AF:

0.000958

GnomAD3 exomes

AF:

0.000688

AC:

173

AN:

251352

Hom.:

AF XY:

0.000685

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000347

Gnomad ASJ exome

AF:

0.0000993

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000457

Gnomad FIN exome

AF:

0.00203

Gnomad NFE exome

AF:

0.000809

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000579

AC:

846

AN:

1461884

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

410

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000383

Gnomad4 FIN exome

AF:

0.00204

Gnomad4 NFE exome

AF:

0.000560

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.000525

AC:

AN:

152290

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.000831

Gnomad4 FIN

AF:

0.00160

Gnomad4 NFE

AF:

0.000647

Gnomad4 OTH

AF:

0.000948

Alfa

AF:

0.000658

Hom.:

Bravo

AF:

0.000389

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.000824

AC:

100

EpiCase

AF:

0.000927

EpiControl

AF:

0.00119

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 02, 2021

The c.457G>A (p.D153N) alteration is located in exon 3 (coding exon 3) of the SIDT2 gene. This alteration results from a G to A substitution at nucleotide position 457, causing the aspartic acid (D) at amino acid position 153 to be replaced by an asparagine (N). 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

0.059

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.67

Cadd

Benign

Dann

Uncertain

0.98

DEOGEN2

Benign

0.011

T;T;T;T;T;.;.

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.57

FATHMM_MKL

Benign

0.59

M_CAP

Benign

0.0028

MetaRNN

Benign

0.0074

T;T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.95

N;N;.;.;.;.;.

MutationTaster

Benign

0.97

N;N;N

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.94

N;.;N;.;N;N;N

REVEL

Benign

0.11

Sift

Benign

0.40

T;.;T;.;T;T;T

Sift4G

Benign

0.49

T;T;T;T;T;T;.

Polyphen

0.0020

B;B;B;B;B;.;.

Vest4

0.17

MVP

0.26

MPC

0.52

ClinPred

0.032

GERP RS

0.18

Varity_R

0.020

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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