chr3-113606309-T-C

Variant names:

• chr3-113606309-T-C
• rs11706066
• NM_017699.3:c.1405-732T>C

Variant summary

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

The NM_001322294.2(SIDT1):​c.1405-732T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 152,022 control chromosomes in the GnomAD database, including 7,291 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.

• Frequency:
  • Genomes: 𝑓 0.29 (7291 hom., cov: 32)
  • Exomes 𝑓: 0.33 (0 hom.)
• Consequence: SIDT1 NM_001322294.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 1 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: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.407 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322294.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIDT1	NM_017699.3	MANE Select	c.1405-732T>C		intron	N/A	NP_060169.2
	SIDT1	NM_001322294.2		c.1405-732T>C		intron	N/A	NP_001309223.1
	SIDT1	NM_001308350.2		c.1405-732T>C		intron	N/A	NP_001295279.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SIDT1	ENST00000264852.9	TSL:2 MANE Select	c.1405-732T>C		intron	N/A	ENSP00000264852.4
	SIDT1	ENST00000393830.5	TSL:1	c.1405-732T>C		intron	N/A	ENSP00000377416.4
	SIDT1	ENST00000950250.1		c.1447-732T>C		intron	N/A	ENSP00000620309.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44350 AN: 151898 Hom.: 7281 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.370

Gnomad SAS AF: 0.422

Gnomad FIN AF: 0.394

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.349

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.333 AC: 2 AN: 6 Hom.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1 AN: 2

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AC: 0 AN: 0

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000037155), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.292 AC: 44385 AN: 152016 Hom.: 7291 Cov.: 32 AF XY: 0.294 AC XY: 21855 AN XY: 74266

African (AFR) AF: 0.149 AC: 6174 AN: 41494

American (AMR) AF: 0.313 AC: 4790 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 820 AN: 3470

East Asian (EAS) AF: 0.369 AC: 1902 AN: 5150

South Asian (SAS) AF: 0.422 AC: 2033 AN: 4816

European-Finnish (FIN) AF: 0.394 AC: 4155 AN: 10542

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.349 AC: 23686 AN: 67940

Other (OTH) AF: 0.274 AC: 579 AN: 2110

Alfa AF: 0.323 Hom.: 12165

Bravo AF: 0.281

Asia WGS AF: 0.412 AC: 1429 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.7
DANN	Benign	0.51
PhyloP100		0.042
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: rs11706066; hg19: chr3-113325156;