rs1060503612

Variant names:

• chr14-95131520-T-C
• rs1060503612
• NM_177438.3:c.427A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-95131520-T-C
• chr14-95131520-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001395691.1(DICER1):​c.-32A>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DICER1 NM_001395691.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.242
• Publications: 1 publications found

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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.02711615).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001395691.1. 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
	DICER1	NM_177438.3	MANE Select	c.427A>G	p.Thr143Ala	missense	Exon 4 of 27	NP_803187.1	Q9UPY3-1
	DICER1	NM_001395691.1		c.-32A>G		5_prime_UTR_premature_start_codon_gain	Exon 4 of 27	NP_001382620.1
	DICER1	NM_001395697.1		c.-1142A>G		5_prime_UTR_premature_start_codon_gain	Exon 6 of 29	NP_001382626.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DICER1	ENST00000343455.8	TSL:1 MANE Select	c.427A>G	p.Thr143Ala	missense	Exon 4 of 27	ENSP00000343745.3	Q9UPY3-1
	DICER1	ENST00000393063.6	TSL:1	c.427A>G	p.Thr143Ala	missense	Exon 6 of 29	ENSP00000376783.1	Q9UPY3-1
	DICER1	ENST00000527414.5	TSL:1	c.427A>G	p.Thr143Ala	missense	Exon 4 of 27	ENSP00000435681.1	Q9UPY3-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251340 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	DICER1-related tumor predisposition (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.057
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.4
DANN	Benign	0.69
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.027	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	-0.99	N
PhyloP100		-0.24
PrimateAI	Benign	0.25	T
PROVEAN	Benign	0.22	N
REVEL	Benign	0.067
Sift	Benign	0.79	T
Sift4G	Benign	0.76	T
Polyphen		0.0	B
Vest4		0.10
MutPred		0.45		Loss of stability (P = 0.0865)
MVP		0.28
MPC		0.48
ClinPred		0.020	T
GERP RS		-0.34
Varity_R		0.081
gMVP		0.12
Mutation Taster		=91/9	polymorphism

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: rs1060503612; hg19: chr14-95597857; COSMIC: COSV105915825;