14-20892057-C-G

Variant names:

• chr14-20892057-C-G
• rs2073342
• NM_002935.3:c.371C>G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_002935.3(RNASE3):​c.371C>G​(p.Thr124Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 1,611,768 control chromosomes in the GnomAD database, including 420,323 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.65 (34417 hom., cov: 30)
  • Exomes 𝑓: 0.72 (385906 hom.)
• Consequence: RNASE3 NM_002935.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.14

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]

LOC100507513 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASE3	NM_002935.3	c.371C>G	p.Thr124Arg	missense_variant	Exon 2 of 2	ENST00000304639.4	NP_002926.2
LOC100507513	XR_110261.4	n.723-16314G>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASE3	ENST00000304639.4	c.371C>G	p.Thr124Arg	missense_variant	Exon 2 of 2	1	NM_002935.3	ENSP00000302324.3

Frequencies

GnomAD3 genomes AF: 0.655 AC: 98433 AN: 150342 Hom.: 34395 Cov.: 30

Gnomad AFR AF: 0.419

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.773

Gnomad ASJ AF: 0.717

Gnomad EAS AF: 0.732

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.799

Gnomad MID AF: 0.707

Gnomad NFE AF: 0.732

Gnomad OTH AF: 0.676

GnomAD3 exomes AF: 0.725 AC: 182236 AN: 251208 Hom.: 67778 AF XY: 0.724 AC XY: 98301 AN XY: 135802

Gnomad AFR exome AF: 0.413

Gnomad AMR exome AF: 0.857

Gnomad ASJ exome AF: 0.714

Gnomad EAS exome AF: 0.721

Gnomad SAS exome AF: 0.687

Gnomad FIN exome AF: 0.804

Gnomad NFE exome AF: 0.726

Gnomad OTH exome AF: 0.731

GnomAD4 exome AF: 0.724 AC: 1057712 AN: 1461306 Hom.: 385906 Cov.: 62 AF XY: 0.723 AC XY: 525724 AN XY: 727018

Gnomad4 AFR exome AF: 0.411

Gnomad4 AMR exome AF: 0.847

Gnomad4 ASJ exome AF: 0.715

Gnomad4 EAS exome AF: 0.742

Gnomad4 SAS exome AF: 0.687

Gnomad4 FIN exome AF: 0.801

Gnomad4 NFE exome AF: 0.728

Gnomad4 OTH exome AF: 0.714

GnomAD4 genome AF: 0.655 AC: 98489 AN: 150462 Hom.: 34417 Cov.: 30 AF XY: 0.658 AC XY: 48398 AN XY: 73550

Gnomad4 AFR AF: 0.418

Gnomad4 AMR AF: 0.773

Gnomad4 ASJ AF: 0.717

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.694

Gnomad4 FIN AF: 0.799

Gnomad4 NFE AF: 0.732

Gnomad4 OTH AF: 0.677

Alfa AF: 0.712 Hom.: 27292

Bravo AF: 0.640

TwinsUK AF: 0.718 AC: 2663

ALSPAC AF: 0.726 AC: 2798

ESP6500AA AF: 0.442 AC: 1936

ESP6500EA AF: 0.717 AC: 6170

ExAC AF: 0.715 AC: 86695

Asia WGS AF: 0.703 AC: 2445 AN: 3478

EpiCase AF: 0.712

EpiControl AF: 0.709

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.044
BayesDel_addAF	Benign	-0.75	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.035
DANN	Benign	0.11
DEOGEN2	Benign	0.063	T
Eigen	Benign	-2.7
Eigen_PC	Benign	-2.6
FATHMM_MKL	Benign	0.00027	N
LIST_S2	Benign	0.11	T
MetaRNN	Benign	0.0000042	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.9	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	3.9	N
REVEL	Benign	0.057
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.042
MPC		0.043
ClinPred		0.00087	T
GERP RS		-3.4
Varity_R		0.046
gMVP		0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.31		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.31		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2073342; hg19: chr14-21360216; COSMIC: COSV58959715;