NM_001024822.4:c.160G>C

Variant names:

• chr14-20590564-C-G
• rs770702429
• NM_001024822.4:c.160G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001024822.4(RNASE12):​c.160G>C​(p.Val54Leu) 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. 16/22 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. V54I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNASE12 NM_001024822.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 0 publications found

Genes affected

RNASE12 (HGNC:24211): (ribonuclease A family member 12 (inactive)) Predicted to enable nucleic acid binding activity. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000259060 (HGNC:):

RNASE11 (HGNC:19269): (ribonuclease A family member 11 (inactive)) Predicted to enable endonuclease activity and nucleic acid binding activity. Predicted to be involved in nucleic acid phosphodiester bond hydrolysis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

RNASE11-AS1 (HGNC:27381): (RNASE11 and RNASE12 antisense RNA 1)

ACMG classification

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=0.0403533).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001024822.4. 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
	RNASE12	NM_001024822.4	MANE Select	c.160G>C	p.Val54Leu	missense	Exon 2 of 2	NP_001019993.1	Q5GAN4
	RNASE11-AS1	NR_122043.1		n.223C>G		non_coding_transcript_exon	Exon 2 of 5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASE12	ENST00000696784.1	MANE Select	c.160G>C	p.Val54Leu	missense	Exon 2 of 2	ENSP00000512867.1	Q5GAN4
	ENSG00000259060	ENST00000555283.1	TSL:4	c.131+29G>C		intron	N/A	ENSP00000477006.1	V9GYQ6
	RNASE12	ENST00000556526.1	TSL:6	c.160G>C	p.Val54Leu	missense	Exon 1 of 1	ENSP00000450580.1	Q5GAN4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	7.4
DANN	Benign	0.64
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.040	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-1.1
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.62	N
REVEL	Benign	0.17
Sift	Benign	0.30	T
Sift4G	Benign	0.59	T
Polyphen		0.0	B
Vest4		0.081
MutPred		0.56		Gain of catalytic residue at R53 (P = 0.0053)
MVP		0.030
MPC		0.010
ClinPred		0.12	T
GERP RS		-6.5
PromoterAI		0.028	Neutral
Varity_R		0.057
gMVP		0.62
Mutation Taster		=96/4	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: rs770702429; hg19: chr14-21058723;