6-166929627-G-A

Variant names:

• chr6-166929627-G-A
• NM_003730.6:c.732C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_003730.6(RNASET2):​c.732C>T​(p.Gly244Gly) variant causes a synonymous 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. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RNASET2 NM_003730.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00500
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 6-166929627-G-A is Benign according to our data. Variant chr6-166929627-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 1932645.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.005 with no splicing effect.

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.732C>T	p.Gly244Gly	synonymous	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.732C>T	p.Gly244Gly	synonymous	Exon 9 of 9	ENSP00000426455.2	O00584-1
	ENSG00000249141	ENST00000507747.1	TSL:5	c.432+4464C>T		intron	N/A	ENSP00000426906.1	H0YAE9
	RNASET2	ENST00000870284.1		c.870C>T	p.Gly290Gly	synonymous	Exon 10 of 10	ENSP00000540343.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.3
DANN	Benign	0.88
PhyloP100		0.0050
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

hg19: chr6-167343115;