6-166929711-C-T

Variant names:

• chr6-166929711-C-T
• rs35517174
• NM_003730.6:c.648G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003730.6(RNASET2):​c.648G>A​(p.Pro216Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0119 in 1,614,046 control chromosomes in the GnomAD database, including 1,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P216P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.041 (360 hom., cov: 33)
  • Exomes 𝑓: 0.0088 (673 hom.)
• Consequence: RNASET2 NM_003730.6 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.91
• Publications: 10 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: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 6-166929711-C-T is Benign according to our data. Variant chr6-166929711-C-T is described in ClinVar as Benign. ClinVar VariationId is 356029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.

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.648G>A	p.Pro216Pro	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.648G>A	p.Pro216Pro	synonymous	Exon 9 of 9	ENSP00000426455.2	O00584-1
	ENSG00000249141	ENST00000507747.1	TSL:5	c.432+4380G>A		intron	N/A	ENSP00000426906.1	H0YAE9
	RNASET2	ENST00000870284.1		c.786G>A	p.Pro262Pro	synonymous	Exon 10 of 10	ENSP00000540343.1

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 6296 AN: 152068 Hom.: 358 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.0780

Gnomad SAS AF: 0.0230

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00141

Gnomad OTH AF: 0.0288

GnomAD2 exomes AF: 0.0189 AC: 4762 AN: 251412 AF XY: 0.0167

Gnomad AFR exome AF: 0.135

Gnomad AMR exome AF: 0.00945

Gnomad ASJ exome AF: 0.00347

Gnomad EAS exome AF: 0.0688

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00109

Gnomad OTH exome AF: 0.0124

GnomAD4 exome AF: 0.00884 AC: 12921 AN: 1461860 Hom.: 673 Cov.: 31 AF XY: 0.00886 AC XY: 6444 AN XY: 727236

African (AFR) AF: 0.138 AC: 4632 AN: 33480

American (AMR) AF: 0.0103 AC: 462 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00356 AC: 93 AN: 26136

East Asian (EAS) AF: 0.0992 AC: 3940 AN: 39700

South Asian (SAS) AF: 0.0223 AC: 1921 AN: 86258

European-Finnish (FIN) AF: 0.000262 AC: 14 AN: 53390

Middle Eastern (MID) AF: 0.00728 AC: 42 AN: 5768

European-Non Finnish (NFE) AF: 0.000738 AC: 821 AN: 1112008

Other (OTH) AF: 0.0165 AC: 996 AN: 60396

GnomAD4 genome AF: 0.0415 AC: 6313 AN: 152186 Hom.: 360 Cov.: 33 AF XY: 0.0409 AC XY: 3042 AN XY: 74398

African (AFR) AF: 0.127 AC: 5258 AN: 41490

American (AMR) AF: 0.0184 AC: 281 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.0781 AC: 404 AN: 5170

South Asian (SAS) AF: 0.0233 AC: 112 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00141 AC: 96 AN: 68028

Other (OTH) AF: 0.0308 AC: 65 AN: 2108

Alfa AF: 0.0161 Hom.: 262

Bravo AF: 0.0468

Asia WGS AF: 0.0670 AC: 233 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.00101

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cystic leukoencephalopathy without megalencephaly (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.011
DANN	Benign	0.59
PhyloP100		-2.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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: rs35517174; hg19: chr6-167343199; COSMIC: COSV50351288; COSMIC: COSV50351288;