11-117181503-G-C

Position:

• chr11-117181503-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040455.2(SIDT2):​c.271G>C​(p.Val91Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,866 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SIDT2 NM_001040455.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.16

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09873989).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SIDT2	NM_001040455.2	c.271G>C	p.Val91Leu	missense_variant	2/26	ENST00000324225.9	NP_001035545.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SIDT2	ENST00000324225.9	c.271G>C	p.Val91Leu	missense_variant	2/26	1	NM_001040455.2	ENSP00000314023.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461866 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 727242

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: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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

Oct 08, 2024

The c.271G>C (p.V91L) alteration is located in exon 2 (coding exon 2) of the SIDT2 gene. This alteration results from a G to C substitution at nucleotide position 271, causing the valine (V) at amino acid position 91 to be replaced by a leucine (L). 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	0.28
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	23
DANN	Benign	0.87
DEOGEN2	Benign	0.0039	T;T;T;T;T;T
Eigen	Benign	-0.31
Eigen_PC	Benign	-0.052
FATHMM_MKL	Benign	0.59	D
LIST_S2	Uncertain	0.93	.;D;D;.;D;D
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.099	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.41	N;.;N;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	0.89	N;N;.;N;.;N
REVEL	Benign	0.11
Sift	Benign	1.0	T;T;.;T;.;T
Sift4G	Benign	1.0	T;T;T;T;T;T
Polyphen		0.0010	B;.;B;B;B;B
Vest4		0.30
MutPred		0.37		Loss of catalytic residue at V91 (P = 0.0103);Loss of catalytic residue at V91 (P = 0.0103);Loss of catalytic residue at V91 (P = 0.0103);Loss of catalytic residue at V91 (P = 0.0103);Loss of catalytic residue at V91 (P = 0.0103);Loss of catalytic residue at V91 (P = 0.0103);
MVP		0.21
MPC		0.53
ClinPred		0.45	T
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: chr11-117052219;