Genetic Variant RNASE13:p.Pro3Ala (chr14-21034282-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001012264.4(RNASE13):c.7C>G(p.Pro3Ala) 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. 17/22 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. P3S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RNASE13
NM_001012264.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.398

Publications

0 publications found

Variant links:

Genes affected

RNASE13 (HGNC:25285): (ribonuclease A family member 13 (inactive)) Predicted to enable nucleic acid binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

RNASE13 links:

NDRG2 (HGNC:14460): (NDRG family member 2) This gene is a member of the N-myc downregulated gene family which belongs to the alpha/beta hydrolase superfamily. The protein encoded by this gene is a cytoplasmic protein that may play a role in neurite outgrowth. This gene may be involved in glioblastoma carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2017]

NDRG2 links:

TPPP2 (HGNC:19293): (tubulin polymerization promoting protein family member 2) Enables tubulin binding activity. Involved in regulation of flagellated sperm motility. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TPPP2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.060305357).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001012264.4. 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
	RNASE13	NM_001012264.4	MANE Select	c.7C>G	p.Pro3Ala	missense	Exon 2 of 2	NP_001012264.1	Q5GAN3
	NDRG2	NM_001282211.2		c.25-10961C>G		intron	N/A	NP_001269140.1	Q9UN36-6

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNASE13	ENST00000382951.4	TSL:1 MANE Select	c.7C>G	p.Pro3Ala	missense	Exon 2 of 2	ENSP00000372410.3	Q5GAN3
NDRG2	ENST00000876704.1		c.-6-10961C>G		intron	N/A	ENSP00000546763.1
NDRG2	ENST00000876707.1		c.-6-10961C>G		intron	N/A	ENSP00000546766.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000408

AC:

AN:

245184

AF XY:

0.00000753

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000473

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.050

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Benign

4.2

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.020

Eigen

Benign

-0.87

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.25

M_CAP

Benign

0.035

MetaRNN

Benign

0.060

MetaSVM

Benign

-0.62

MutationAssessor

Benign

1.4

PhyloP100

-0.40

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.5

REVEL

Benign

0.19

Sift

Benign

0.11

Sift4G

Benign

0.096

Polyphen

0.011

Vest4

0.16

MutPred

0.26

Gain of helix (P = 0.0349)

MVP

0.42

MPC

0.015

ClinPred

0.018

GERP RS

-0.22

Varity_R

0.053

gMVP

0.20

Mutation Taster

=97/3

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over