rs3777722

Variant names:

• chr6-166938616-C-A
• rs3777722
• NM_003730.6:c.446+279G>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 22 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: Ambry Genetics, Illumina, Orphanet, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000249141 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.446+279G>T		intron	N/A	NP_003721.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASET2	ENST00000508775.6	TSL:1 MANE Select	c.446+279G>T		intron	N/A	ENSP00000426455.2	O00584-1
	ENSG00000249141	ENST00000507747.1	TSL:5	c.386+279G>T		intron	N/A	ENSP00000426906.1	H0YAE9
	RNASET2	ENST00000870284.1		c.446+279G>T		intron	N/A	ENSP00000540343.1

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

GnomAD2 exomes AF: 0.176 AC: 42647 AN: 242290 AF XY: 0.174

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 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

African (AFR) AF: 0.0383 AC: 598 AN: 15616

American (AMR) AF: 0.295 AC: 12047 AN: 40794

Ashkenazi Jewish (ASJ) AF: 0.0742 AC: 1340 AN: 18062

East Asian (EAS) AF: 0.369 AC: 9942 AN: 26976

South Asian (SAS) AF: 0.288 AC: 19593 AN: 68132

European-Finnish (FIN) AF: 0.179 AC: 7602 AN: 42488

Middle Eastern (MID) AF: 0.0855 AC: 316 AN: 3696

European-Non Finnish (NFE) AF: 0.0854 AC: 24968 AN: 292308

Other (OTH) AF: 0.131 AC: 3590 AN: 27468

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

African (AFR) AF: 0.0390 AC: 1622 AN: 41540

American (AMR) AF: 0.200 AC: 3061 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0811 AC: 281 AN: 3466

East Asian (EAS) AF: 0.402 AC: 2071 AN: 5158

South Asian (SAS) AF: 0.310 AC: 1492 AN: 4818

European-Finnish (FIN) AF: 0.189 AC: 1999 AN: 10580

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0851 AC: 5782 AN: 67982

Other (OTH) AF: 0.123 AC: 260 AN: 2112

Alfa AF: 0.0953 Hom.: 3338

Bravo AF: 0.109

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
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
PhyloP100		0.037
Sift4G	Uncertain	0.031	D
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3777722;

hg19: chr6-167352104;

COSMIC: COSV50351087;