rs771697618

chr14-95107680-C-Achr14-95107680-C-T

Variant summary

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

The NM_177438.3(DICER1):c.2732G>T(p.Ser911Ile) variant causes a missense 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. 13/21 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. S911G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DICER1 NM_177438.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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 where missense usually causes diseases, DICER1
• BP4: Computational evidence support a benign effect (MetaRNN=0.16606054).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DICER1	NM_177438.3	c.2732G>T	p.Ser911Ile	missense_variant	17/27	ENST00000343455.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DICER1	ENST00000343455.8	c.2732G>T	p.Ser911Ile	missense_variant	17/27	1	NM_177438.3	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	0.14
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	23
Dann	Uncertain	0.99
DEOGEN2	Benign	0.11	T;T;T;T;.
Eigen	Benign	-0.10
Eigen_PC	Benign	0.032
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.41	N;N;N;N;N
MutationTaster	Benign	0.99	D;D;D;D;D
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.41	N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.24	T;T;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		0.60	P;P;P;P;.
Vest4		0.36
MutPred		0.48		Loss of disorder (P = 0.011);Loss of disorder (P = 0.011);Loss of disorder (P = 0.011);Loss of disorder (P = 0.011);Loss of disorder (P = 0.011);
MVP		0.48
MPC		0.86
ClinPred		0.41	T
GERP RS		4.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.58

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-95574017; COSMIC: COSV58615577; COSMIC: COSV58615577;