rs146168332

Variant names:

• chr14-20511099-C-T
• rs146168332
• NM_001386206.3:c.628C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-20511099-C-T
• chr14-20511099-C-A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001386206.3(RNASE10):​c.628C>T​(p.Arg210Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000569 in 1,494,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: RNASE10 NM_001386206.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.67
• Publications: 0 publications found

Genes affected

RNASE10 (HGNC:19275): (ribonuclease A family member 10 (inactive)) Predicted to enable nucleic acid binding activity. Predicted to be involved in several processes, including heterotypic cell-cell adhesion; positive regulation of flagellated sperm motility; and regulation of fertilization. Predicted to act upstream of or within epithelial cell morphogenesis; seminiferous tubule development; and single fertilization. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.044210702).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386206.3. 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
	RNASE10	NM_001386206.3	MANE Select	c.628C>T	p.Arg210Cys	missense	Exon 2 of 2	NP_001373135.2	Q5GAN6-1
	RNASE10	NM_001012975.3		c.628C>T	p.Arg210Cys	missense	Exon 2 of 2	NP_001012993.1	Q5GAN6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASE10	ENST00000430083.2	TSL:2 MANE Select	c.628C>T	p.Arg210Cys	missense	Exon 2 of 2	ENSP00000392996.2	Q5GAN6-1
	RNASE10	ENST00000328444.6	TSL:6	c.628C>T	p.Arg210Cys	missense	Exon 1 of 1	ENSP00000333358.5	Q5GAN6-1

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152210 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000296 AC: 5 AN: 168646 AF XY: 0.0000447

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000600

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000581 AC: 78 AN: 1342538 Hom.: 0 Cov.: 32 AF XY: 0.0000611 AC XY: 40 AN XY: 654724

African (AFR) AF: 0.000101 AC: 3 AN: 29790

American (AMR) AF: 0.00 AC: 0 AN: 27198

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19620

East Asian (EAS) AF: 0.00 AC: 0 AN: 37932

South Asian (SAS) AF: 0.0000308 AC: 2 AN: 64982

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48870

Middle Eastern (MID) AF: 0.000191 AC: 1 AN: 5248

European-Non Finnish (NFE) AF: 0.0000664 AC: 70 AN: 1053706

Other (OTH) AF: 0.0000362 AC: 2 AN: 55192

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152210 Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4 AN XY: 74368

African (AFR) AF: 0.0000241 AC: 1 AN: 41440

American (AMR) AF: 0.00 AC: 0 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68046

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000993 Hom.: 0

Bravo AF: 0.0000756

ExAC AF: 0.0000338 AC: 4

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	1.0
DANN	Benign	0.68
DEOGEN2	Benign	0.012	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.010	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.044	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-1.7
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.27	N
REVEL	Benign	0.11
Sift	Uncertain	0.020	D
Sift4G	Benign	0.087	T
Polyphen		0.017	B
Vest4		0.15
MVP		0.030
MPC		0.0086
ClinPred		0.058	T
GERP RS		-5.3
Varity_R		0.055
gMVP		0.51
Mutation Taster		=99/1	polymorphism

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: rs146168332; hg19: chr14-20979258; COSMIC: COSV60517378;