rs9459805

Variant names:

• chr6-166922663-A-G
• rs9459805
• NM_003730.6:c.*6925T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003730.6(RNASET2):​c.*6925T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 152,166 control chromosomes in the GnomAD database, including 8,253 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (8253 hom., cov: 33)
• Consequence: RNASET2 NM_003730.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.777
• Publications: 3 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, PanelApp Australia, Orphanet

ENSG00000249141 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASET2	NM_003730.6	c.*6925T>C		3_prime_UTR_variant	Exon 9 of 9	ENST00000508775.6	NP_003721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASET2	ENST00000508775.6	c.*6925T>C		3_prime_UTR_variant	Exon 9 of 9	1	NM_003730.6	ENSP00000426455.2
ENSG00000249141	ENST00000507747.1	c.432+11428T>C		intron_variant	Intron 7 of 7	5		ENSP00000426906.1

Frequencies

GnomAD3 genomes AF: 0.270 AC: 41045 AN: 152048 Hom.: 8215 Cov.: 33

Gnomad AFR AF: 0.572

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.217

Gnomad EAS AF: 0.0983

Gnomad SAS AF: 0.201

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.247

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.270 AC: 41139 AN: 152166 Hom.: 8253 Cov.: 33 AF XY: 0.266 AC XY: 19769 AN XY: 74386

African (AFR) AF: 0.572 AC: 23733 AN: 41468

American (AMR) AF: 0.164 AC: 2506 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.217 AC: 755 AN: 3472

East Asian (EAS) AF: 0.0980 AC: 508 AN: 5184

South Asian (SAS) AF: 0.201 AC: 972 AN: 4832

European-Finnish (FIN) AF: 0.125 AC: 1322 AN: 10598

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10521 AN: 67998

Other (OTH) AF: 0.250 AC: 528 AN: 2110

Alfa AF: 0.213 Hom.: 2433

Bravo AF: 0.286

Asia WGS AF: 0.217 AC: 758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.1
DANN	Benign	0.63
PhyloP100		-0.78

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: rs9459805; hg19: chr6-167336151;