rs3777722

Positions:

• chr6-166938616-C-A
• chr6-166938616-C-G
• chr6-166938616-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003730.6(RNASET2):​c.446+279G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 687,686 control chromosomes in the GnomAD database, including 10,582 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 0.11 (1552 hom., cov: 33)
  • Exomes 𝑓: 0.15 (9030 hom.)
• Consequence: RNASET2 NM_003730.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0370

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003393352).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASET2	NM_003730.6	c.446+279G>T		intron_variant		ENST00000508775.6	NP_003721.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASET2	ENST00000508775.6	c.446+279G>T		intron_variant		1	NM_003730.6	ENSP00000426455.2
ENSG00000249141	ENST00000507747.1	c.386+279G>T		intron_variant		5		ENSP00000426906.1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16652 AN: 152028 Hom.: 1550 Cov.: 33

Gnomad AFR AF: 0.0391

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.0811

Gnomad EAS AF: 0.403

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0851

Gnomad OTH AF: 0.119

GnomAD3 exomes AF: 0.176 AC: 42647 AN: 242290 Hom.: 5619 AF XY: 0.174 AC XY: 23082 AN XY: 132954

Gnomad AFR exome AF: 0.0387

Gnomad AMR exome AF: 0.305

Gnomad ASJ exome AF: 0.0729

Gnomad EAS exome AF: 0.418

Gnomad SAS exome AF: 0.294

Gnomad FIN exome AF: 0.185

Gnomad NFE exome AF: 0.0884

Gnomad OTH exome AF: 0.140

GnomAD4 exome AF: 0.149 AC: 79996 AN: 535540 Hom.: 9030 Cov.: 0 AF XY: 0.154 AC XY: 45496 AN XY: 294866

Gnomad4 AFR exome AF: 0.0383

Gnomad4 AMR exome AF: 0.295

Gnomad4 ASJ exome AF: 0.0742

Gnomad4 EAS exome AF: 0.369

Gnomad4 SAS exome AF: 0.288

Gnomad4 FIN exome AF: 0.179

Gnomad4 NFE exome AF: 0.0854

Gnomad4 OTH exome AF: 0.131

GnomAD4 genome AF: 0.110 AC: 16676 AN: 152146 Hom.: 1552 Cov.: 33 AF XY: 0.120 AC XY: 8929 AN XY: 74372

Gnomad4 AFR AF: 0.0390

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.0811

Gnomad4 EAS AF: 0.402

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.0851

Gnomad4 OTH AF: 0.123

Alfa AF: 0.0913 Hom.: 1415

Bravo AF: 0.109

TwinsUK AF: 0.0823 AC: 305

ALSPAC AF: 0.0732 AC: 282

ESP6500AA AF: 0.0428 AC: 75

ESP6500EA AF: 0.0826 AC: 329

ExAC AF: 0.167 AC: 19816

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.89	T
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.45
DEOGEN2	Benign	0.0095	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.17	T
MetaRNN	Benign	0.0034	T
MetaSVM	Benign	-1.0	T
Sift4G	Uncertain	0.031	D
Vest4		0.34
ClinPred		0.00095	T
GERP RS		0.20

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: rs3777722; hg19: chr6-167352104; COSMIC: COSV50351087;