5-31532322-A-T

Variant names:

• chr5-31532322-A-T
• rs2291109
• NM_018356.3:c.-71A>T

Variant summary

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

The NM_018356.3(C5orf22):​c.-71A>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.98 in 1,531,754 control chromosomes in the GnomAD database, including 736,551 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 0.98 (72990 hom., cov: 31)
  • Exomes 𝑓: 0.98 (663561 hom.)
• Consequence: C5orf22 NM_018356.3 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.992
• Publications: 13 publications found

Genes affected

C5orf22 (HGNC:25639): (chromosome 5 open reading frame 22)

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.99 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C5orf22	NM_018356.3	c.-71A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 9	ENST00000325366.14	NP_060826.2
C5orf22	NM_018356.3	c.-71A>T		5_prime_UTR_variant	Exon 1 of 9	ENST00000325366.14	NP_060826.2
DROSHA	NM_001382508.1	c.-582T>A		upstream_gene_variant		ENST00000344624.8	NP_001369437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
C5orf22	ENST00000325366.14	c.-71A>T		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 9	1	NM_018356.3	ENSP00000326879.9
C5orf22	ENST00000325366.14	c.-71A>T		5_prime_UTR_variant	Exon 1 of 9	1	NM_018356.3	ENSP00000326879.9
DROSHA	ENST00000344624.8	c.-582T>A		upstream_gene_variant		5	NM_001382508.1	ENSP00000339845.3

Frequencies

GnomAD3 genomes AF: 0.979 AC: 148814 AN: 152054 Hom.: 72935 Cov.: 31

Gnomad AFR AF: 0.998

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.966

Gnomad ASJ AF: 0.996

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.951

Gnomad FIN AF: 0.926

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.992

Gnomad OTH AF: 0.978

GnomAD4 exome AF: 0.980 AC: 1351962 AN: 1379582 Hom.: 663561 Cov.: 21 AF XY: 0.979 AC XY: 676355 AN XY: 690722

African (AFR) AF: 0.998 AC: 31483 AN: 31538

American (AMR) AF: 0.944 AC: 42004 AN: 44480

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 25431 AN: 25544

East Asian (EAS) AF: 0.785 AC: 30761 AN: 39206

South Asian (SAS) AF: 0.951 AC: 80239 AN: 84370

European-Finnish (FIN) AF: 0.928 AC: 48926 AN: 52726

Middle Eastern (MID) AF: 0.983 AC: 5097 AN: 5184

European-Non Finnish (NFE) AF: 0.993 AC: 1031950 AN: 1039034

Other (OTH) AF: 0.975 AC: 56071 AN: 57500

GnomAD4 genome AF: 0.979 AC: 148926 AN: 152172 Hom.: 72990 Cov.: 31 AF XY: 0.974 AC XY: 72468 AN XY: 74380

African (AFR) AF: 0.998 AC: 41459 AN: 41550

American (AMR) AF: 0.965 AC: 14764 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.996 AC: 3459 AN: 3472

East Asian (EAS) AF: 0.807 AC: 4111 AN: 5096

South Asian (SAS) AF: 0.951 AC: 4578 AN: 4816

European-Finnish (FIN) AF: 0.926 AC: 9823 AN: 10610

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.992 AC: 67463 AN: 68018

Other (OTH) AF: 0.977 AC: 2066 AN: 2114

Alfa AF: 0.984 Hom.: 8612

Bravo AF: 0.981

Asia WGS AF: 0.894 AC: 3112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.3
DANN	Benign	0.54
PhyloP100		-0.99
PromoterAI		0.0020	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2291109; hg19: chr5-31532429;