rs1060503600

Variant names:

• chr14-95126623-G-A
• NM_177438.3:c.860C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-95126623-G-A
• chr14-95126623-G-C

Variant summary

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

The NM_001395697.1(DICER1):​c.-709C>T variant causes a 5 prime UTR premature start codon gain change. 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_001395697.1 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.13

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=0.27372512).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DICER1	NM_177438.3	c.860C>T	p.Ser287Phe	missense_variant	Exon 7 of 27	ENST00000343455.8	NP_803187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DICER1	ENST00000343455.8	c.860C>T	p.Ser287Phe	missense_variant	Exon 7 of 27	1	NM_177438.3	ENSP00000343745.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Hereditary cancer-predisposing syndrome Uncertain:1

Nov 17, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The p.S287F variant (also known as c.860C>T), located in coding exon 6 of the DICER1 gene, results from a C to T substitution at nucleotide position 860. The serine at codon 287 is replaced by phenylalanine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Benign	0.96
DEOGEN2	Benign	0.34	T;T;T;T;.
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.59
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.89	.;.;D;.;D
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.27	T;T;T;T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	0.79	N;N;N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-0.91	N;N;N;N;N
REVEL	Benign	0.14
Sift	Benign	0.16	T;T;T;T;T
Sift4G	Uncertain	0.022	D;D;D;D;D
Polyphen		0.88	P;P;P;P;.
Vest4		0.40
MutPred		0.45		Loss of disorder (P = 0.0081);Loss of disorder (P = 0.0081);Loss of disorder (P = 0.0081);Loss of disorder (P = 0.0081);Loss of disorder (P = 0.0081);
MVP		0.56
MPC		0.79
ClinPred		0.60	D
GERP RS		5.4
Varity_R		0.14
gMVP		0.35

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: chr14-95592960;