3-113581336-A-T

Variant names:

• chr3-113581336-A-T
• rs2271494
• NM_017699.3:c.664-25A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000264852.9(SIDT1):​c.664-25A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.442 in 1,591,484 control chromosomes in the GnomAD database, including 159,831 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.46 (17044 hom., cov: 31)
  • Exomes 𝑓: 0.44 (142787 hom.)
• Consequence: SIDT1 ENST00000264852.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 14 publications found

Genes affected

SIDT1 (HGNC:25967): (SID1 transmembrane family member 1) The protein encoded by this gene belongs to SID1 family of transmembrane dsRNA-gated channels. Family members transport dsRNA into cells and are required for systemic RNA interference. [provided by RefSeq, May 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000264852.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIDT1	NM_017699.3	MANE Select	c.664-25A>T		intron	N/A	NP_060169.2
	SIDT1	NM_001322294.2		c.664-25A>T		intron	N/A	NP_001309223.1
	SIDT1	NM_001308350.2		c.664-25A>T		intron	N/A	NP_001295279.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIDT1	ENST00000264852.9	TSL:2 MANE Select	c.664-25A>T		intron	N/A	ENSP00000264852.4
	SIDT1	ENST00000393830.5	TSL:1	c.664-25A>T		intron	N/A	ENSP00000377416.4
	SIDT1	ENST00000491730.5	TSL:5	n.1131-25A>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70496 AN: 151650 Hom.: 17021 Cov.: 31

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.443

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.777

Gnomad SAS AF: 0.474

Gnomad FIN AF: 0.479

Gnomad MID AF: 0.423

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.449

GnomAD2 exomes AF: 0.461 AC: 115464 AN: 250654 AF XY: 0.460

Gnomad AFR exome AF: 0.522

Gnomad AMR exome AF: 0.359

Gnomad ASJ exome AF: 0.481

Gnomad EAS exome AF: 0.773

Gnomad FIN exome AF: 0.482

Gnomad NFE exome AF: 0.423

Gnomad OTH exome AF: 0.451

GnomAD4 exome AF: 0.439 AC: 632503 AN: 1439714 Hom.: 142787 Cov.: 27 AF XY: 0.441 AC XY: 316160 AN XY: 717648

African (AFR) AF: 0.528 AC: 17464 AN: 33078

American (AMR) AF: 0.368 AC: 16415 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.473 AC: 12311 AN: 26018

East Asian (EAS) AF: 0.804 AC: 31822 AN: 39584

South Asian (SAS) AF: 0.476 AC: 40877 AN: 85862

European-Finnish (FIN) AF: 0.486 AC: 25796 AN: 53100

Middle Eastern (MID) AF: 0.472 AC: 2698 AN: 5712

European-Non Finnish (NFE) AF: 0.419 AC: 457810 AN: 1091996

Other (OTH) AF: 0.457 AC: 27310 AN: 59702

GnomAD4 genome AF: 0.465 AC: 70569 AN: 151770 Hom.: 17044 Cov.: 31 AF XY: 0.468 AC XY: 34686 AN XY: 74164

African (AFR) AF: 0.519 AC: 21459 AN: 41334

American (AMR) AF: 0.378 AC: 5762 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1697 AN: 3470

East Asian (EAS) AF: 0.777 AC: 3994 AN: 5142

South Asian (SAS) AF: 0.475 AC: 2288 AN: 4812

European-Finnish (FIN) AF: 0.479 AC: 5030 AN: 10502

Middle Eastern (MID) AF: 0.424 AC: 123 AN: 290

European-Non Finnish (NFE) AF: 0.425 AC: 28880 AN: 67950

Other (OTH) AF: 0.444 AC: 932 AN: 2100

Alfa AF: 0.459 Hom.: 3022

Bravo AF: 0.461

Asia WGS AF: 0.556 AC: 1935 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.8
DANN	Benign	0.71
PhyloP100		0.26
BranchPoint Hunter		3.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2271494; hg19: chr3-113300183;