14-20891927-G-A

Variant names:

• chr14-20891927-G-A
• rs768722970
• NM_002935.3:c.241G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002935.3(RNASE3):​c.241G>A​(p.Val81Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. V81F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RNASE3 NM_002935.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.241G>A	p.Val81Ile	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.241G>A	p.Val81Ile	missense	Exon 2 of 2	ENSP00000302324.3	P12724
	ENSG00000259130	ENST00000717679.1		n.259-16184C>T		intron	N/A
	ENSG00000259130	ENST00000717680.1		n.347-16184C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 47

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Uncertain	0.98
DEOGEN2	Benign	0.096	T
Eigen	Benign	-0.91
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0075	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0018	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.63
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.92	N
REVEL	Benign	0.054
Sift	Uncertain	0.025	D
Sift4G	Benign	0.093	T
Polyphen		0.21	B
Vest4		0.031
MutPred		0.73		Loss of MoRF binding (P = 0.1767)
MVP		0.17
MPC		0.051
ClinPred		0.12	T
GERP RS		-2.0
Varity_R		0.35
gMVP		0.73
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs768722970; hg19: chr14-21360086;