rs1060503654

Positions:

• chr14-95103600-C-A
• chr14-95103600-C-G
• chr14-95103600-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The ENST00000343455.8(DICER1):​c.3796G>T​(p.Asp1266Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1266E) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DICER1 ENST00000343455.8 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.14

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), DICER1. . Gene score misZ 4.2261 (greater than the threshold 3.09). Trascript score misZ 6.1353 (greater than threshold 3.09). GenCC has associacion of gene with goiter, multinodular 1, with or without Sertoli-Leydig cell tumors, global developmental delay - lung cysts - overgrowth - Wilms tumor syndrome, DICER1-related tumor predisposition, DICER1 syndrome, pleuropulmonary blastoma.
• BP4: Computational evidence support a benign effect (MetaRNN=0.16443339).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DICER1	NM_177438.3	c.3796G>T	p.Asp1266Tyr	missense_variant	21/27	ENST00000343455.8	NP_803187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DICER1	ENST00000343455.8	c.3796G>T	p.Asp1266Tyr	missense_variant	21/27	1	NM_177438.3	ENSP00000343745	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.00030	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.35	T;T;T;T;.;.
Eigen	Benign	-0.57
Eigen_PC	Benign	-0.43
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.74	.;.;T;.;T;T
M_CAP	Benign	0.050	D
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.1	L;L;L;L;.;L
MutationTaster	Benign	1.0	N;N;N;N;N;N
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.4	N;N;N;N;N;N
REVEL	Benign	0.10
Sift	Uncertain	0.012	D;D;D;D;D;D
Sift4G	Uncertain	0.013	D;D;D;D;D;D
Polyphen		0.010	B;B;B;B;.;.
Vest4		0.35
MutPred		0.40		Loss of disorder (P = 0.0174);Loss of disorder (P = 0.0174);Loss of disorder (P = 0.0174);Loss of disorder (P = 0.0174);.;Loss of disorder (P = 0.0174);
MVP		0.80
MPC		0.65
ClinPred		0.33	T
GERP RS		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.070
gMVP		0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-95569937;