chr6-166929610-G-T

Variant names:

• chr6-166929610-G-T
• rs754430788
• NM_003730.6:c.749C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_003730.6(RNASET2):​c.749C>A​(p.Pro250Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,158 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 33)
• Consequence: RNASET2 NM_003730.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.61

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34508476).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASET2	NM_003730.6	c.749C>A	p.Pro250Gln	missense_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.749C>A	p.Pro250Gln	missense_variant	Exon 9 of 9	1	NM_003730.6	ENSP00000426455.2
ENSG00000249141	ENST00000507747.1	c.432+4481C>A		intron_variant	Intron 7 of 7	5		ENSP00000426906.1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152158 Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1 AN XY: 74318

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	0.0024	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	.;T;T;T;T
Eigen	Benign	0.17
Eigen_PC	Benign	0.060
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.74	T;.;T;T;T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.35	T;T;T;T;T
MetaSVM	Benign	-0.84	T
MutationAssessor	Uncertain	2.5	.;M;.;M;.
PrimateAI	Benign	0.31	T
PROVEAN	Pathogenic	-4.9	D;D;.;D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0020	D;D;.;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;.
Polyphen		1.0	.;D;.;D;.
Vest4		0.35
MutPred		0.47		.;Loss of glycosylation at P250 (P = 0.0013);.;Loss of glycosylation at P250 (P = 0.0013);Loss of glycosylation at P250 (P = 0.0013);
MVP		0.76
MPC		0.80
ClinPred		0.99	D
GERP RS		3.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.63
gMVP		0.72

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: rs754430788; hg19: chr6-167343098;