5-31400896-T-C

Variant names:

• chr5-31400896-T-C
• rs642321
• NM_001382508.1:c.*536A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001382508.1(DROSHA):​c.*536A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 156,732 control chromosomes in the GnomAD database, including 44,978 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 0.76 (43733 hom., cov: 33)
  • Exomes 𝑓: 0.72 (1245 hom.)
• Consequence: DROSHA NM_001382508.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.52
• Publications: 17 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.805 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	NM_001382508.1	MANE Select	c.*536A>G		3_prime_UTR	Exon 36 of 36	NP_001369437.1
	DROSHA	NM_013235.5		c.*536A>G		3_prime_UTR	Exon 35 of 35	NP_037367.3
	DROSHA	NM_001100412.2		c.*536A>G		3_prime_UTR	Exon 35 of 35	NP_001093882.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DROSHA	ENST00000344624.8	TSL:5 MANE Select	c.*536A>G		3_prime_UTR	Exon 36 of 36	ENSP00000339845.3
	DROSHA	ENST00000511367.6	TSL:1	c.*536A>G		3_prime_UTR	Exon 35 of 35	ENSP00000425979.2
	DROSHA	ENST00000513349.5	TSL:1	c.*536A>G		downstream_gene	N/A	ENSP00000424161.1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114893 AN: 152026 Hom.: 43720 Cov.: 33

Gnomad AFR AF: 0.720

Gnomad AMI AF: 0.721

Gnomad AMR AF: 0.715

Gnomad ASJ AF: 0.705

Gnomad EAS AF: 0.523

Gnomad SAS AF: 0.677

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.734

Gnomad NFE AF: 0.810

Gnomad OTH AF: 0.758

GnomAD4 exome AF: 0.723 AC: 3319 AN: 4588 Hom.: 1245 Cov.: 0 AF XY: 0.713 AC XY: 1902 AN XY: 2666

African (AFR) AF: 0.650 AC: 26 AN: 40

American (AMR) AF: 0.611 AC: 187 AN: 306

Ashkenazi Jewish (ASJ) AF: 0.609 AC: 39 AN: 64

East Asian (EAS) AF: 0.494 AC: 78 AN: 158

South Asian (SAS) AF: 0.589 AC: 297 AN: 504

European-Finnish (FIN) AF: 0.728 AC: 131 AN: 180

Middle Eastern (MID) AF: 0.750 AC: 6 AN: 8

European-Non Finnish (NFE) AF: 0.772 AC: 2424 AN: 3138

Other (OTH) AF: 0.689 AC: 131 AN: 190

GnomAD4 genome AF: 0.756 AC: 114947 AN: 152144 Hom.: 43733 Cov.: 33 AF XY: 0.751 AC XY: 55840 AN XY: 74392

African (AFR) AF: 0.720 AC: 29861 AN: 41492

American (AMR) AF: 0.715 AC: 10925 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.705 AC: 2446 AN: 3470

East Asian (EAS) AF: 0.522 AC: 2700 AN: 5172

South Asian (SAS) AF: 0.679 AC: 3273 AN: 4818

European-Finnish (FIN) AF: 0.773 AC: 8190 AN: 10594

Middle Eastern (MID) AF: 0.724 AC: 213 AN: 294

European-Non Finnish (NFE) AF: 0.810 AC: 55084 AN: 67990

Other (OTH) AF: 0.755 AC: 1597 AN: 2116

Alfa AF: 0.789 Hom.: 60423

Bravo AF: 0.749

Asia WGS AF: 0.582 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.71
PhyloP100		-2.5
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: rs642321; hg19: chr5-31401003;