6-166949985-C-T

Variant names:

• chr6-166949985-C-T
• rs3798305
• NM_003730.6:c.148-1360G>A

Variant summary

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

The NM_003730.6(RNASET2):​c.148-1360G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0415 in 152,356 control chromosomes in the GnomAD database, including 246 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 0.042 (246 hom., cov: 33)
• Consequence: RNASET2 NM_003730.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.781
• Publications: 6 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0944 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASET2	NM_003730.6	c.148-1360G>A		intron_variant	Intron 2 of 8	ENST00000508775.6	NP_003721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASET2	ENST00000508775.6	c.148-1360G>A		intron_variant	Intron 2 of 8	1	NM_003730.6	ENSP00000426455.2
ENSG00000249141	ENST00000507747.1	c.88-1360G>A		intron_variant	Intron 2 of 7	5		ENSP00000426906.1

Frequencies

GnomAD3 genomes AF: 0.0414 AC: 6310 AN: 152238 Hom.: 244 Cov.: 33

Gnomad AFR AF: 0.0966

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.0257

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.0875

Gnomad SAS AF: 0.0374

Gnomad FIN AF: 0.00489

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.0157

Gnomad OTH AF: 0.0368

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

GnomAD4 genome AF: 0.0415 AC: 6330 AN: 152356 Hom.: 246 Cov.: 33 AF XY: 0.0417 AC XY: 3107 AN XY: 74506

African (AFR) AF: 0.0969 AC: 4028 AN: 41574

American (AMR) AF: 0.0256 AC: 392 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0202 AC: 70 AN: 3470

East Asian (EAS) AF: 0.0875 AC: 454 AN: 5190

South Asian (SAS) AF: 0.0372 AC: 180 AN: 4834

European-Finnish (FIN) AF: 0.00489 AC: 52 AN: 10626

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0156 AC: 1064 AN: 68036

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

Alfa AF: 0.0294 Hom.: 267

Bravo AF: 0.0460

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.80
DANN	Benign	0.19
PhyloP100		0.78
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: rs3798305; hg19: chr6-167363473;