NM_003730.6:c.715A>G

Variant names:

• chr6-166929644-T-C
• rs1583211839
• NM_003730.6:c.715A>G

Variant summary

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

The NM_003730.6(RNASET2):​c.715A>G​(p.Arg239Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNASET2 NM_003730.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.622
• Publications: 0 publications found

Genes affected

RNASET2 (HGNC:21686): (ribonuclease T2) This ribonuclease gene is a novel member of the Rh/T2/S-glycoprotein class of extracellular ribonucleases. It is a single copy gene that maps to 6q27, a region associated with human malignancies and chromosomal rearrangement. [provided by RefSeq, Jul 2008]

RNASET2 Gene-Disease associations (from GenCC):

• cystic leukoencephalopathy without megalencephaly

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet, Illumina

ENSG00000249141 (HGNC:):

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=0.038077354).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003730.6. 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
	RNASET2	NM_003730.6	MANE Select	c.715A>G	p.Arg239Gly	missense	Exon 9 of 9	NP_003721.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASET2	ENST00000508775.6	TSL:1 MANE Select	c.715A>G	p.Arg239Gly	missense	Exon 9 of 9	ENSP00000426455.2	O00584-1
	ENSG00000249141	ENST00000507747.1	TSL:5	c.432+4447A>G		intron	N/A	ENSP00000426906.1	H0YAE9
	RNASET2	ENST00000870284.1		c.853A>G	p.Arg285Gly	missense	Exon 10 of 10	ENSP00000540343.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.1
DANN	Benign	0.58
DEOGEN2	Benign	0.0070	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.62
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.11
Sift	Benign	0.40	T
Sift4G	Benign	0.36	T
Polyphen		0.42	B
Vest4		0.095
MutPred		0.36		Gain of loop (P = 0.0166)
MVP		0.20
MPC		0.31
ClinPred		0.23	T
GERP RS		-9.1
Varity_R		0.20
gMVP		0.45
Mutation Taster		=91/9	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: rs1583211839; hg19: chr6-167343132;