Variant 20-62413496-C-T 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.1580G>A(p.Gly527Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000586 in 1,364,328 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: not found (cov: 34)

Exomes 𝑓: 0.0000059 ( 0 hom. )

Consequence

RBBP8NL
NM_080833.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.10

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=0.06447744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBBP8NL	NM_080833.3 linkuse as main transcript	c.1580G>A	p.Gly527Asp	missense_variant	11/14	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.1580G>A	p.Gly527Asp	missense_variant	11/14	2	NM_080833.3	ENSP00000252998.1		Q8NC74

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000574

AC:

AN:

174178

Hom.:

AF XY:

0.0000105

AC XY:

AN XY:

95554

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000586

AC:

AN:

1364328

Hom.:

Cov.:

AF XY:

0.00000743

AC XY:

AN XY:

672668

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000653

Gnomad4 OTH exome

AF:

0.0000179

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000827

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

Oct 26, 2024

The c.1580G>A (p.G527D) alteration is located in exon 11 (coding exon 10) of the RBBP8NL gene. This alteration results from a G to A substitution at nucleotide position 1580, causing the glycine (G) at amino acid position 527 to be replaced by an aspartic acid (D). 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

0.10

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.6

DANN

Benign

0.92

DEOGEN2

Benign

0.0080

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.35

M_CAP

Benign

0.014

MetaRNN

Benign

0.064

MetaSVM

Benign

-0.98

MutationAssessor

Benign

2.0

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.070

REVEL

Benign

0.013

Sift

Benign

0.31

Sift4G

Benign

0.41

Polyphen

0.42

Vest4

0.12

MutPred

0.17

Gain of solvent accessibility (P = 0.0638);

MVP

0.076

MPC

0.12

ClinPred

0.28

GERP RS

-0.49

Varity_R

0.072

gMVP

0.12

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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