Genetic Variant NM_017699.3:c.1405-732T>C (chr3-113606309-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_017699.3(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_017699.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0420

Publications

1 publications found

Variant links:

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]

SIDT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SIDT1	NM_017699.3 link	c.1405-732T>C		intron_variant	Intron 14 of 24	ENST00000264852.9	NP_060169.2	Q9NXL6-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SIDT1	ENST00000264852.9 link	c.1405-732T>C	intron_variant	Intron 14 of 24	2	NM_017699.3	ENSP00000264852.4	Q9NXL6-1
SIDT1	ENST00000393830.5 link	c.1405-732T>C	intron_variant	Intron 14 of 25	1		ENSP00000377416.4	Q9NXL6-2
SIDT1	ENST00000463226.1 link	n.314+1333T>C	intron_variant	Intron 4 of 14	2
SIDT1	ENST00000492863.1 link	n.-103T>C	upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.292

AC:

44350

AN:

151898

Hom.:

7281

Cov.:

show subpopulations

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:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

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

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.500

AC:

AN:

Other (OTH)

AC:

AN:

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.292

AC:

44385

AN:

152016

Hom.:

7291

Cov.:

AF XY:

0.294

AC XY:

21855

AN XY:

74266

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.349

AC:

23686

AN:

67940

Other (OTH)

AF:

0.274

AC:

579

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1559

3118

4676

6235

7794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

474

948

1422

1896

2370

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

4.7

(source)

DANN

Benign

0.51

PhyloP100

0.042

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over