Variant 20-62413993-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_080833.3(RBBP8NL):c.1358A>G(p.Gln453Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000409 in 1,418,256 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. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000041 ( 0 hom. )

Consequence

RBBP8NL
NM_080833.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.342

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 -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.008568734).

BP6

Variant 20-62413993-T-C is Benign according to our data. Variant chr20-62413993-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3313121.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBBP8NL	NM_080833.3 linkuse as main transcript	c.1358A>G	p.Gln453Arg	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.1358A>G	p.Gln453Arg	missense_variant	10/14	2	NM_080833.3	ENSP00000252998.1		Q8NC74

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000442

AC:

AN:

181046

Hom.:

AF XY:

0.0000305

AC XY:

AN XY:

98206

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000570

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000409

AC:

AN:

1418256

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

701514

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00153

Gnomad4 SAS exome

AF:

0.0000124

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000509

Hom.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000761

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 16, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.58

DANN

Benign

0.10

DEOGEN2

Benign

0.00037

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0013

LIST_S2

Benign

0.33

M_CAP

Benign

0.0025

MetaRNN

Benign

0.0086

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-1.4

PrimateAI

Benign

0.22

PROVEAN

Benign

0.21

REVEL

Benign

0.014

Sift

Benign

1.0

Sift4G

Benign

0.71

Polyphen

0.0

Vest4

0.032

MutPred

0.15

Gain of MoRF binding (P = 0.0109);

MVP

0.014

MPC

0.060

ClinPred

0.0065

GERP RS

1.5

Varity_R

0.030

gMVP

0.055

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