NM_001382508.1:c.3597C>T

Variant names:

• chr5-31410816-G-A
• rs61748189
• NM_001382508.1:c.3597C>T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001382508.1(DROSHA):​c.3597C>T​(p.Tyr1199Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,613,926 control chromosomes in the GnomAD database, including 129 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0078 (13 hom., cov: 33)
  • Exomes 𝑓: 0.010 (116 hom.)
• Consequence: DROSHA NM_001382508.1 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.524
• Publications: 6 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 5-31410816-G-A is Benign according to our data. Variant chr5-31410816-G-A is described in ClinVar as Benign. ClinVar VariationId is 776037.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.524 with no splicing effect.
• BS2: High AC in GnomAd4 at 1188 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.3597C>T	p.Tyr1199Tyr	synonymous	Exon 31 of 36	NP_001369437.1	Q9NRR4-1
	DROSHA	NM_013235.5		c.3597C>T	p.Tyr1199Tyr	synonymous	Exon 30 of 35	NP_037367.3
	DROSHA	NM_001100412.2		c.3486C>T	p.Tyr1162Tyr	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.3597C>T	p.Tyr1199Tyr	synonymous	Exon 31 of 36	ENSP00000339845.3	Q9NRR4-1
	DROSHA	ENST00000511367.6	TSL:1	c.3597C>T	p.Tyr1199Tyr	synonymous	Exon 30 of 35	ENSP00000425979.2	Q9NRR4-1
	DROSHA	ENST00000513349.5	TSL:1	c.3486C>T	p.Tyr1162Tyr	synonymous	Exon 30 of 35	ENSP00000424161.1	Q9NRR4-4

Frequencies

GnomAD3 genomes AF: 0.00780 AC: 1187 AN: 152202 Hom.: 13 Cov.: 33

Gnomad AFR AF: 0.00215

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00857

Gnomad ASJ AF: 0.0386

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0100

Gnomad OTH AF: 0.00958

GnomAD2 exomes AF: 0.00849 AC: 2115 AN: 249034 AF XY: 0.00813

Gnomad AFR exome AF: 0.00258

Gnomad AMR exome AF: 0.00663

Gnomad ASJ exome AF: 0.0331

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0106

Gnomad NFE exome AF: 0.0107

Gnomad OTH exome AF: 0.00910

GnomAD4 exome AF: 0.0105 AC: 15328 AN: 1461606 Hom.: 116 Cov.: 30 AF XY: 0.0101 AC XY: 7360 AN XY: 727092

African (AFR) AF: 0.00170 AC: 57 AN: 33478

American (AMR) AF: 0.00695 AC: 311 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.0322 AC: 841 AN: 26132

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39696

South Asian (SAS) AF: 0.00109 AC: 94 AN: 86256

European-Finnish (FIN) AF: 0.0105 AC: 560 AN: 53402

Middle Eastern (MID) AF: 0.00347 AC: 20 AN: 5768

European-Non Finnish (NFE) AF: 0.0115 AC: 12791 AN: 1111792

Other (OTH) AF: 0.0108 AC: 653 AN: 60364

GnomAD4 genome AF: 0.00780 AC: 1188 AN: 152320 Hom.: 13 Cov.: 33 AF XY: 0.00764 AC XY: 569 AN XY: 74482

African (AFR) AF: 0.00214 AC: 89 AN: 41566

American (AMR) AF: 0.00856 AC: 131 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0386 AC: 134 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.0121 AC: 129 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0100 AC: 683 AN: 68036

Other (OTH) AF: 0.00948 AC: 20 AN: 2110

Alfa AF: 0.00981 Hom.: 18

Bravo AF: 0.00793

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.0116

EpiControl AF: 0.0130

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	DROSHA-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	0.27
DANN	Benign	0.56
PhyloP100		-0.52
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs61748189; hg19: chr5-31410923;