rs2073342

Positions:

• chr14-20892057-C-A
• chr14-20892057-C-G
• chr14-20892057-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002935.3(RNASE3):​c.371C>A​(p.Thr124Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. T124R) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 30)
• 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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08301753).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASE3	NM_002935.3	c.371C>A	p.Thr124Lys	missense_variant	2/2	ENST00000304639.4	NP_002926.2
LOC100507513	XR_110261.4	n.723-16314G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASE3	ENST00000304639.4	c.371C>A	p.Thr124Lys	missense_variant	2/2	1	NM_002935.3	ENSP00000302324.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.017
DANN	Benign	0.30
DEOGEN2	Benign	0.062	T
Eigen	Benign	-2.4
Eigen_PC	Benign	-2.4
FATHMM_MKL	Benign	0.00061	N
LIST_S2	Benign	0.097	T
M_CAP	Benign	0.0091	T
MetaRNN	Benign	0.083	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-1.0	N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	2.5	N
REVEL	Benign	0.056
Sift	Benign	0.095	T
Sift4G	Benign	0.32	T
Polyphen		0.0	B
Vest4		0.052
MutPred		0.41		Gain of methylation at T124 (P = 0.0013);
MVP		0.26
MPC		0.044
ClinPred		0.086	T
GERP RS		-3.4
Varity_R		0.044
gMVP		0.79

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: rs2073342; hg19: chr14-21360216;