rs1555376190

Variant names:

• chr14-95131619-C-G
• NM_177438.3:c.328G>C

Your query was ambiguous. Multiple possible variants found:

• chr14-95131619-C-G
• chr14-95131619-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001395691.1(DICER1):​c.-131G>C variant causes a 5 prime UTR premature start codon gain change. The variant allele was found at a frequency of 0.000000684 in 1,461,626 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DICER1 NM_001395691.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.83

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
• BP4: Computational evidence support a benign effect (MetaRNN=0.30271405).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DICER1	NM_177438.3	c.328G>C	p.Val110Leu	missense_variant	Exon 4 of 27	ENST00000343455.8	NP_803187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DICER1	ENST00000343455.8	c.328G>C	p.Val110Leu	missense_variant	Exon 4 of 27	1	NM_177438.3	ENSP00000343745.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461626 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727138

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.33
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T;T;T;.
Eigen	Benign	-0.026
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.94	.;.;D;.;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.30	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.76	N;N;N;N;N
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-0.69	N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.033	D;D;D;D;T
Sift4G	Benign	0.39	T;T;T;T;T
Polyphen		0.034	B;B;B;B;.
Vest4		0.41
MutPred		0.52		Loss of MoRF binding (P = 0.1151);Loss of MoRF binding (P = 0.1151);Loss of MoRF binding (P = 0.1151);Loss of MoRF binding (P = 0.1151);Loss of MoRF binding (P = 0.1151);
MVP		0.58
MPC		0.60
ClinPred		0.75	D
GERP RS		5.7
Varity_R		0.41
gMVP		0.65

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: chr14-95597956;