11-117183860-T-G

Position:

• chr11-117183860-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001040455.2(SIDT2):​c.784T>G​(p.Phe262Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SIDT2 NM_001040455.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.58

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 (HGNC:):

ACMG classification

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=0.28592917).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIDT2	NM_001040455.2	c.784T>G	p.Phe262Val	missense_variant	7/26	ENST00000324225.9	NP_001035545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIDT2	ENST00000324225.9	c.784T>G	p.Phe262Val	missense_variant	7/26	1	NM_001040455.2	ENSP00000314023.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 02, 2024

The c.784T>G (p.F262V) alteration is located in exon 7 (coding exon 7) of the SIDT2 gene. This alteration results from a T to G substitution at nucleotide position 784, causing the phenylalanine (F) at amino acid position 262 to be replaced by a valine (V). 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	0.14
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.017	T;T;T;T;T;.
Eigen	Benign	0.011
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	.;T;.;T;T;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.29	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L;.;.;.;.
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.0	N;.;N;.;N;N
REVEL	Benign	0.066
Sift	Benign	0.047	D;.;D;.;D;D
Sift4G	Benign	0.29	T;T;T;T;T;T
Polyphen		0.13	B;B;B;B;B;.
Vest4		0.48
MutPred		0.65		Gain of sheet (P = 0.0507);Gain of sheet (P = 0.0507);Gain of sheet (P = 0.0507);Gain of sheet (P = 0.0507);Gain of sheet (P = 0.0507);.;
MVP		0.37
MPC		0.94
ClinPred		0.48	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.13
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-117054576;