chr6-166929644-T-C

Position:

• chr6-166929644-T-C

Variant summary

Our verdict is Likely benign. Variant got -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. 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.

• 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

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]

ENSG00000249141 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.038077354).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASET2	NM_003730.6	c.715A>G	p.Arg239Gly	missense_variant	9/9	ENST00000508775.6	NP_003721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASET2	ENST00000508775.6	c.715A>G	p.Arg239Gly	missense_variant	9/9	1	NM_003730.6	ENSP00000426455.2
ENSG00000249141	ENST00000507747.1	c.432+4447A>G		intron_variant		5		ENSP00000426906.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 27, 2024

The c.715A>G (p.R239G) alteration is located in exon 9 (coding exon 9) of the RNASET2 gene. This alteration results from a A to G substitution at nucleotide position 715, causing the arginine (R) at amino acid position 239 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0082	N
LIST_S2	Benign	0.73	T;.;T;T;T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.038	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	.;L;.;L;.
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-1.0	N;N;.;N;N
REVEL	Benign	0.11
Sift	Benign	0.40	T;T;.;T;T
Sift4G	Benign	0.36	T;T;T;T;.
Polyphen		0.42	.;B;.;B;.
Vest4		0.095
MutPred		0.36		.;Gain of loop (P = 0.0166);.;Gain of loop (P = 0.0166);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

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: rs1583211839; hg19: chr6-167343132;