NM_177438.3:c.830C>T

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_177438.3(DICER1):c.830C>T(p.Ala277Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000316 in 1,580,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A277S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

DICER1
NM_177438.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:6

Conservation

PhyloP100: 9.00

Publications

0 publications found

Variant links:

Genes affected

DICER1 (HGNC:17098): (dicer 1, ribonuclease III) This gene encodes a protein possessing an RNA helicase motif containing a DEXH box in its amino terminus and an RNA motif in the carboxy terminus. The encoded protein functions as a ribonuclease and is required by the RNA interference and small temporal RNA (stRNA) pathways to produce the active small RNA component that represses gene expression. This protein also acts as a strong antiviral agent with activity against RNA viruses, including the Zika and SARS-CoV-2 viruses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2021]

DICER1 Gene-Disease associations (from GenCC):

DICER1-related tumor predisposition
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
pleuropulmonary blastoma
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
DICER1 syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

DICER1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_177438.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DICER1	NM_177438.3	MANE Select	c.830C>T	p.Ala277Val	missense	Exon 7 of 27	NP_803187.1	Q9UPY3-1
DICER1	NM_001271282.3		c.830C>T	p.Ala277Val	missense	Exon 7 of 27	NP_001258211.1	Q9UPY3-1
DICER1	NM_001291628.2		c.830C>T	p.Ala277Val	missense	Exon 7 of 27	NP_001278557.1	Q9UPY3-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DICER1	ENST00000343455.8	TSL:1 MANE Select	c.830C>T	p.Ala277Val	missense	Exon 7 of 27	ENSP00000343745.3	Q9UPY3-1
DICER1	ENST00000393063.6	TSL:1	c.830C>T	p.Ala277Val	missense	Exon 9 of 29	ENSP00000376783.1	Q9UPY3-1
DICER1	ENST00000527414.5	TSL:1	c.830C>T	p.Ala277Val	missense	Exon 7 of 27	ENSP00000435681.1	Q9UPY3-1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251262

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000280

AC:

AN:

1427996

Hom.:

Cov.:

AF XY:

0.00000281

AC XY:

AN XY:

712436

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32704

American (AMR)

AF:

0.0000224

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25950

East Asian (EAS)

AF:

0.00

AC:

AN:

39436

South Asian (SAS)

AF:

0.00

AC:

AN:

85534

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5686

European-Non Finnish (NFE)

AF:

0.00000277

AC:

AN:

1081272

Other (OTH)

AF:

0.00

AC:

AN:

59342

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000658

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10560

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000113

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

DICER1-related tumor predisposition (1)

Global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome (1)

Hereditary cancer-predisposing syndrome (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Pathogenic

0.75

Eigen_PC

Pathogenic

0.75

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.047

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.7

PhyloP100

9.0

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-1.3

REVEL

Benign

0.20

Sift

Benign

0.15

Sift4G

Benign

0.26

Polyphen

0.99

Vest4

0.64

MutPred

0.43

Gain of helix (P = 0.0078)

MVP

0.65

MPC

1.4

ClinPred

0.83

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.53

gMVP

0.55

Mutation Taster

=31/69

disease causing

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over