Variant chr22-45414002-A-G 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_015653.5(RIBC2):c.116A>G(p.Asn39Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,551,558 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/15 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: 𝑓 0.00020 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

RIBC2
NM_015653.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.148

Variant links:

Genes affected

RIBC2 (HGNC:13241): (RIB43A domain with coiled-coils 2) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

RIBC2 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=0.036131263).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RIBC2	NM_015653.5 link	c.116A>G	p.Asn39Ser	missense_variant	1/7	ENST00000614167.2	NP_056468.3	Q9H4K1
RIBC2	XM_017028766.2 link	c.116A>G	p.Asn39Ser	missense_variant	1/5		XP_016884255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RIBC2	ENST00000614167.2 link	c.116A>G	p.Asn39Ser	missense_variant	1/7	1	NM_015653.5	ENSP00000483356.1		Q9H4K1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000520

AC:

AN:

153960

Hom.:

AF XY:

0.0000490

AC XY:

AN XY:

81686

show subpopulations

Gnomad AFR exome

AF:

0.00101

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1399298

Hom.:

Cov.:

AF XY:

0.00000724

AC XY:

AN XY:

690152

show subpopulations

Gnomad4 AFR exome

AF:

0.000696

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.000197

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000193

Hom.:

Bravo

AF:

0.000204

ESP6500AA

AF:

0.00145

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000379

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

Nov 13, 2024

The c.101A>G (p.N34S) alteration is located in exon 1 (coding exon 1) of the RIBC2 gene. This alteration results from a A to G substitution at nucleotide position 101, causing the asparagine (N) at amino acid position 34 to be replaced by a serine (S). 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

0.086

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.012

Eigen

Benign

-0.32

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.63

M_CAP

Benign

0.0038

MetaRNN

Benign

0.036

MetaSVM

Benign

-1.0

PrimateAI

Uncertain

0.50

Sift4G

Benign

0.73

Vest4

0.040

MVP

0.37

ClinPred

0.030

GERP RS

3.2

gMVP

0.20

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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