Variant 20-62414086-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080833.3(RBBP8NL):c.1265C>T(p.Pro422Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,591,864 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

RBBP8NL
NM_080833.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.792

Variant links:

Genes affected

RBBP8NL (HGNC:16144): (RBBP8 N-terminal like) Located in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

RBBP8NL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.031477362).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBBP8NL	NM_080833.3 linkuse as main transcript	c.1265C>T	p.Pro422Leu	missense_variant	10/14	ENST00000252998.2	NP_543023.2	Q8NC74

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBBP8NL	ENST00000252998.2 linkuse as main transcript	c.1265C>T	p.Pro422Leu	missense_variant	10/14	2	NM_080833.3	ENSP00000252998.1		Q8NC74

Frequencies

GnomAD3 genomes

AF:

0.000118

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000115

AC:

AN:

199414

Hom.:

AF XY:

0.0000911

AC XY:

AN XY:

109802

show subpopulations

Gnomad AFR exome

AF:

0.0000894

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000130

Gnomad SAS exome

AF:

0.0000374

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000212

Gnomad OTH exome

AF:

0.000195

GnomAD4 exome

AF:

0.000115

AC:

166

AN:

1439656

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

714754

show subpopulations

Gnomad4 AFR exome

AF:

0.0000604

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000518

Gnomad4 SAS exome

AF:

0.0000240

Gnomad4 FIN exome

AF:

0.0000415

Gnomad4 NFE exome

AF:

0.000140

Gnomad4 OTH exome

AF:

0.0000672

GnomAD4 genome

AF:

0.000118

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000577

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000151

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.000143

AC:

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

Dec 06, 2022

The c.1265C>T (p.P422L) alteration is located in exon 10 (coding exon 9) of the RBBP8NL gene. This alteration results from a C to T substitution at nucleotide position 1265, causing the proline (P) at amino acid position 422 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

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.78

CADD

Benign

5.6

DANN

Benign

0.96

DEOGEN2

Benign

0.055

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.51

M_CAP

Benign

0.0044

MetaRNN

Benign

0.031

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.2

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.0070

Sift

Uncertain

0.025

Sift4G

Uncertain

0.012

Polyphen

0.078

Vest4

0.065

MVP

0.072

MPC

0.060

ClinPred

0.020

GERP RS

-4.0

Varity_R

0.041

gMVP

0.064

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over