11-117186578-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6_Moderate BS2

The NM_001040455.2(SIDT2):c.963-6A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,558,164 control chromosomes in the GnomAD database, including 118 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0079 (8 hom., cov: 31)
  • Exomes 𝑓: 0.012 (110 hom.)
• Consequence: SIDT2 NM_001040455.2 splice_region, splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.0002563
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.172

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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 11-117186578-A-G is Benign according to our data. Variant chr11-117186578-A-G is described in ClinVar as [Benign]. Clinvar id is 789211.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SIDT2	NM_001040455.2	c.963-6A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000324225.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SIDT2	ENST00000324225.9	c.963-6A>G		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001040455.2	P3

Frequencies

GnomAD3 genomes AF: 0.00796 AC: 1210 AN: 152094 Hom.: 8 Cov.: 31

Gnomad AFR AF: 0.00237

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.00349

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0134

Gnomad OTH AF: 0.00765

GnomAD3 exomes AF: 0.00839 AC: 1668 AN: 198912 Hom.: 13 AF XY: 0.00876 AC XY: 923 AN XY: 105364

Gnomad AFR exome AF: 0.00256

Gnomad AMR exome AF: 0.00443

Gnomad ASJ exome AF: 0.0210

Gnomad EAS exome AF: 0.0000604

Gnomad SAS exome AF: 0.00420

Gnomad FIN exome AF: 0.00394

Gnomad NFE exome AF: 0.0129

Gnomad OTH exome AF: 0.00806

GnomAD4 exome AF: 0.0118 AC: 16527 AN: 1405952 Hom.: 110 Cov.: 32 AF XY: 0.0115 AC XY: 7985 AN XY: 695184

Gnomad4 AFR exome AF: 0.00163

Gnomad4 AMR exome AF: 0.00461

Gnomad4 ASJ exome AF: 0.0201

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00529

Gnomad4 FIN exome AF: 0.00403

Gnomad4 NFE exome AF: 0.0135

Gnomad4 OTH exome AF: 0.00932

GnomAD4 genome AF: 0.00794 AC: 1209 AN: 152212 Hom.: 8 Cov.: 31 AF XY: 0.00766 AC XY: 570 AN XY: 74408

Gnomad4 AFR AF: 0.00236

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00498

Gnomad4 FIN AF: 0.00349

Gnomad4 NFE AF: 0.0134

Gnomad4 OTH AF: 0.00757

Alfa AF: 0.0107 Hom.: 4

Bravo AF: 0.00784

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	7.8
Dann	Benign	0.94
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00026
dbscSNV1_RF	Benign	0.030
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

Other links and lift over

dbSNP: rs143730905; hg19: chr11-117057294;