5-31400896-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DROSHA	NM_001382508.1	c.*536A>G		3_prime_UTR_variant	Exon 36 of 36	ENST00000344624.8	NP_001369437.1
DROSHA	NM_013235.5	c.*536A>G		3_prime_UTR_variant	Exon 35 of 35		NP_037367.3
DROSHA	NM_001100412.2	c.*536A>G		3_prime_UTR_variant	Exon 35 of 35		NP_001093882.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DROSHA	ENST00000344624	c.*536A>G		3_prime_UTR_variant	Exon 36 of 36	5	NM_001382508.1	ENSP00000339845.3
DROSHA	ENST00000511367	c.*536A>G		3_prime_UTR_variant	Exon 35 of 35	1		ENSP00000425979.2
DROSHA	ENST00000513349.5	c.*536A>G		downstream_gene_variant		1		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

Gnomad4 AFR exome AF: 0.650

Gnomad4 AMR exome AF: 0.611

Gnomad4 ASJ exome AF: 0.609

Gnomad4 EAS exome AF: 0.494

Gnomad4 SAS exome AF: 0.589

Gnomad4 FIN exome AF: 0.728

Gnomad4 NFE exome AF: 0.772

Gnomad4 OTH exome AF: 0.689

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

Gnomad4 AFR AF: 0.720

Gnomad4 AMR AF: 0.715

Gnomad4 ASJ AF: 0.705

Gnomad4 EAS AF: 0.522

Gnomad4 SAS AF: 0.679

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.810

Gnomad4 OTH AF: 0.755

Alfa AF: 0.792 Hom.: 46532

Bravo AF: 0.749

Asia WGS AF: 0.582 AC: 2028 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.11
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs642321; hg19: chr5-31401003;