rs151169198

Variant names:

• chr14-20891900-C-T
• rs151169198
• NM_002935.3:c.214C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_002935.3(RNASE3):​c.214C>T​(p.Arg72Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00609 in 1,612,940 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R72H) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.0043 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (50 hom.)
• Consequence: RNASE3 NM_002935.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.421
• Publications: 14 publications found

Genes affected

RNASE3 (HGNC:10046): (ribonuclease A family member 3) The protein encoded by this gene belongs to the pancreatic ribonuclease family, a subset of the ribonuclease A superfamily. The protein exhibits antimicrobial activity against pathogenic bacteria [provided by RefSeq, Oct 2014]

ENSG00000259130 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.009386808).
• BP6: Variant 14-20891900-C-T is Benign according to our data. Variant chr14-20891900-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2644053.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002935.3. 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
	RNASE3	NM_002935.3	MANE Select	c.214C>T	p.Arg72Cys	missense	Exon 2 of 2	NP_002926.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASE3	ENST00000304639.4	TSL:1 MANE Select	c.214C>T	p.Arg72Cys	missense	Exon 2 of 2	ENSP00000302324.3	P12724
	ENSG00000259130	ENST00000717679.1		n.259-16157G>A		intron	N/A
	ENSG00000259130	ENST00000717680.1		n.347-16157G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00434 AC: 657 AN: 151212 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00111

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.00341

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00208

Gnomad FIN AF: 0.00179

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00747

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00433 AC: 1089 AN: 251340 AF XY: 0.00428

Gnomad AFR exome AF: 0.00124

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00213

Gnomad NFE exome AF: 0.00792

Gnomad OTH exome AF: 0.00407

GnomAD4 exome AF: 0.00627 AC: 9161 AN: 1461610 Hom.: 50 Cov.: 46 AF XY: 0.00612 AC XY: 4453 AN XY: 727154

African (AFR) AF: 0.000873 AC: 29 AN: 33232

American (AMR) AF: 0.00157 AC: 70 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.000536 AC: 14 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39698

South Asian (SAS) AF: 0.00151 AC: 130 AN: 86250

European-Finnish (FIN) AF: 0.00217 AC: 116 AN: 53418

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5764

European-Non Finnish (NFE) AF: 0.00766 AC: 8521 AN: 1112002

Other (OTH) AF: 0.00450 AC: 272 AN: 60386

GnomAD4 genome AF: 0.00434 AC: 657 AN: 151330 Hom.: 4 Cov.: 32 AF XY: 0.00430 AC XY: 318 AN XY: 73978

African (AFR) AF: 0.00111 AC: 45 AN: 40644

American (AMR) AF: 0.00341 AC: 52 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4814

European-Finnish (FIN) AF: 0.00179 AC: 19 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00747 AC: 508 AN: 68012

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00599 Hom.: 10

Bravo AF: 0.00411

TwinsUK AF: 0.00620 AC: 23

ALSPAC AF: 0.00804 AC: 31

ESP6500AA AF: 0.00137 AC: 6

ESP6500EA AF: 0.00663 AC: 57

ExAC AF: 0.00466 AC: 566

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00616

EpiControl AF: 0.00634

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.37	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.0094	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0020	T
MetaRNN	Benign	0.0094	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.6	L
PhyloP100		-0.42
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.040
Sift	Uncertain	0.0060	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.13
MVP		0.26
MPC		0.27
ClinPred		0.048	T
GERP RS		-0.65
Varity_R		0.41
gMVP		0.84
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs151169198; hg19: chr14-21360059;