5-31410843-T-C

Variant names:

• chr5-31410843-T-C
• rs750285143
• NM_001382508.1:c.3570A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_001382508.1(DROSHA):​c.3570A>G​(p.Val1190Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,640 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: DROSHA NM_001382508.1 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -2.17
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 5-31410843-T-C is Benign according to our data. Variant chr5-31410843-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3054331.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-2.17 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 31 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382508.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	NM_001382508.1	MANE Select	c.3570A>G	p.Val1190Val	synonymous	Exon 31 of 36	NP_001369437.1	Q9NRR4-1
	DROSHA	NM_013235.5		c.3570A>G	p.Val1190Val	synonymous	Exon 30 of 35	NP_037367.3
	DROSHA	NM_001100412.2		c.3459A>G	p.Val1153Val	synonymous	Exon 30 of 35	NP_001093882.1	Q9NRR4-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	ENST00000344624.8	TSL:5 MANE Select	c.3570A>G	p.Val1190Val	synonymous	Exon 31 of 36	ENSP00000339845.3	Q9NRR4-1
	DROSHA	ENST00000511367.6	TSL:1	c.3570A>G	p.Val1190Val	synonymous	Exon 30 of 35	ENSP00000425979.2	Q9NRR4-1
	DROSHA	ENST00000513349.5	TSL:1	c.3459A>G	p.Val1153Val	synonymous	Exon 30 of 35	ENSP00000424161.1	Q9NRR4-4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1461640 Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14 AN XY: 727102

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000279 AC: 31 AN: 1111810

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.00000756

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	DROSHA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	2.3
DANN	Benign	0.61
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs750285143; hg19: chr5-31410950;