5-31401340-A-G

Variant names:

• chr5-31401340-A-G
• rs10719
• NM_001382508.1:c.*92T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001382508.1(DROSHA):​c.*92T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.743 in 1,532,660 control chromosomes in the GnomAD database, including 436,300 homozygotes. 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: 𝑓 0.64 (33986 hom., cov: 32)
  • Exomes 𝑓: 0.75 (402314 hom.)
• Consequence: DROSHA NM_001382508.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.46
• Publications: 96 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=-0.34).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.794 is higher than 0.05.

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.*92T>C		3_prime_UTR	Exon 36 of 36	NP_001369437.1	Q9NRR4-1
	DROSHA	NM_013235.5		c.*92T>C		3_prime_UTR	Exon 35 of 35	NP_037367.3
	DROSHA	NM_001100412.2		c.*92T>C		3_prime_UTR	Exon 35 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.*92T>C		3_prime_UTR	Exon 36 of 36	ENSP00000339845.3	Q9NRR4-1
	DROSHA	ENST00000511367.6	TSL:1	c.*92T>C		3_prime_UTR	Exon 35 of 35	ENSP00000425979.2	Q9NRR4-1
	DROSHA	ENST00000513349.5	TSL:1	c.*92T>C		3_prime_UTR	Exon 35 of 35	ENSP00000424161.1	Q9NRR4-4

Frequencies

GnomAD3 genomes AF: 0.643 AC: 97755 AN: 151964 Hom.: 33984 Cov.: 32

Gnomad AFR AF: 0.394

Gnomad AMI AF: 0.713

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.676

Gnomad EAS AF: 0.318

Gnomad SAS AF: 0.617

Gnomad FIN AF: 0.726

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.800

Gnomad OTH AF: 0.663

GnomAD2 exomes AF: 0.687 AC: 170158 AN: 247826 AF XY: 0.693

Gnomad AFR exome AF: 0.378

Gnomad AMR exome AF: 0.654

Gnomad ASJ exome AF: 0.687

Gnomad EAS exome AF: 0.326

Gnomad FIN exome AF: 0.745

Gnomad NFE exome AF: 0.799

Gnomad OTH exome AF: 0.729

GnomAD4 exome AF: 0.754 AC: 1041601 AN: 1380578 Hom.: 402314 Cov.: 19 AF XY: 0.752 AC XY: 519573 AN XY: 690962

African (AFR) AF: 0.372 AC: 11641 AN: 31272

American (AMR) AF: 0.656 AC: 28723 AN: 43776

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 16963 AN: 24412

East Asian (EAS) AF: 0.277 AC: 10228 AN: 36892

South Asian (SAS) AF: 0.627 AC: 52846 AN: 84230

European-Finnish (FIN) AF: 0.748 AC: 37078 AN: 49572

Middle Eastern (MID) AF: 0.667 AC: 3621 AN: 5428

European-Non Finnish (NFE) AF: 0.801 AC: 840328 AN: 1048598

Other (OTH) AF: 0.712 AC: 40173 AN: 56398

GnomAD4 genome AF: 0.643 AC: 97779 AN: 152082 Hom.: 33986 Cov.: 32 AF XY: 0.638 AC XY: 47403 AN XY: 74330

African (AFR) AF: 0.394 AC: 16328 AN: 41476

American (AMR) AF: 0.669 AC: 10218 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.676 AC: 2346 AN: 3472

East Asian (EAS) AF: 0.318 AC: 1641 AN: 5168

South Asian (SAS) AF: 0.618 AC: 2980 AN: 4820

European-Finnish (FIN) AF: 0.726 AC: 7665 AN: 10554

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.800 AC: 54367 AN: 67996

Other (OTH) AF: 0.658 AC: 1389 AN: 2110

Alfa AF: 0.742 Hom.: 164230

Bravo AF: 0.626

Asia WGS AF: 0.456 AC: 1590 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs10719; hg19: chr5-31401447; COSMIC: COSV60776848; COSMIC: COSV60776848;