rs372814914

Variant names:

• chr5-31410759-C-A
• rs372814914
• NM_001382508.1:c.3654G>T

Your query was ambiguous. Multiple possible variants found:

• chr5-31410759-C-A
• chr5-31410759-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001382508.1(DROSHA):​c.3654G>T​(p.Ala1218Ala) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DROSHA NM_001382508.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.06

Genes affected

DROSHA (HGNC:17904): (drosha ribonuclease III) This gene encodes a ribonuclease (RNase) III double-stranded RNA-specific ribonuclease and subunit of the microprocessor protein complex, which catalyzes the initial processing step of microRNA (miRNA) synthesis. The encoded protein cleaves the stem loop structure from the primary microRNA (pri-miRNA) in the nucleus, yielding the precursor miRNA (pre-miRNA), which is then exported to the cytoplasm for further processing. In a human cell line lacking a functional copy of this gene, canonical miRNA synthesis is reduced. Somatic mutations in this gene have been observed in human patients with kidney cancer. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-3.06 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.3654G>T	p.Ala1218Ala	synonymous_variant	Exon 31 of 36	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.3654G>T	p.Ala1218Ala	synonymous_variant	Exon 30 of 35		NP_037367.3
DROSHA	NM_001100412.2	c.3543G>T	p.Ala1181Ala	synonymous_variant	Exon 30 of 35		NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624.8	c.3654G>T	p.Ala1218Ala	synonymous_variant	Exon 31 of 36	5	NM_001382508.1	ENSP00000339845.3
DROSHA	ENST00000511367.6	c.3654G>T	p.Ala1218Ala	synonymous_variant	Exon 30 of 35	1		ENSP00000425979.2
DROSHA	ENST00000513349.5	c.3543G>T	p.Ala1181Ala	synonymous_variant	Exon 30 of 35	1		ENSP00000424161.1
DROSHA	ENST00000511778.5	n.770G>T		non_coding_transcript_exon_variant	Exon 3 of 8	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.13
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

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

LitVar

Other links and lift over

dbSNP: rs372814914; hg19: chr5-31410866;