Variant 19-10319173-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_133452.3(RAVER1):c.1838G>T(p.Arg613Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,364 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RAVER1
NM_133452.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.48

Variant links:

Genes affected

RAVER1 (HGNC:30296): (ribonucleoprotein, PTB binding 1) Enables RNA binding activity. Predicted to be involved in regulation of alternative mRNA splicing, via spliceosome. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RAVER1 links:

ENSG00000267303 (HGNC:):

ENSG00000267303 links:

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ACMG classification

Classification made for transcript

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=0.40511942).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAVER1	NM_133452.3 link	c.1838G>T	p.Arg613Leu	missense_variant	10/13	ENST00000617231.5	NP_597709.3	Q8IY67
RAVER1	NM_001366174.1 link	c.1763G>T	p.Arg588Leu	missense_variant	11/14		NP_001353103.1
RAVER1	XM_047438143.1 link	c.821G>T	p.Arg274Leu	missense_variant	6/9		XP_047294099.1
RAVER1	XM_047438141.1 link	c.*93G>T		3_prime_UTR_variant	10/10		XP_047294097.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAVER1	ENST00000617231.5 link	c.1838G>T	p.Arg613Leu	missense_variant	10/13	5	NM_133452.3	ENSP00000482277.1		A0A087WZ13
ENSG00000267303	ENST00000586529.1 link	n.92G>T		non_coding_transcript_exon_variant	2/8	5		ENSP00000467814.1		K7EQG2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461364

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 14, 2023

The c.1889G>T (p.R630L) alteration is located in exon 10 (coding exon 10) of the RAVER1 gene. This alteration results from a G to T substitution at nucleotide position 1889, causing the arginine (R) at amino acid position 630 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.019

.;T;T

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.43

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.85

T;.;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Benign

-1.2

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.47

.;N;.

REVEL

Benign

0.11

Sift

Uncertain

0.013

.;D;.

Sift4G

Benign

0.25

T;T;T

Polyphen

0.99

.;D;D

Vest4

0.72

MutPred

0.23

.;Gain of glycosylation at K632 (P = 0.0849);Gain of glycosylation at K632 (P = 0.0849);

MVP

0.14

MPC

0.60

ClinPred

0.92

GERP RS

4.2

gMVP

0.51

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over