Variant 7-5064172-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021163.4(RBAK):c.716G>A(p.Gly239Glu) 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 1,461,608 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict 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

RBAK
NM_021163.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.00

Variant links:

Genes affected

RBAK (HGNC:17680): (RB associated KRAB zinc finger) This gene encodes a nuclear protein which interacts with the tumor suppressor retinoblastoma 1. The two interacting proteins are thought to act as a transcriptional repressor for promoters which are activated by the E2F1 transcription factor. This protein contains a Kruppel-associated box (KRAB), which is a transcriptional repressor motif. Read-through transcripts that include exons from the downstream gene LOC389458 are expressed from this locus. [provided by RefSeq, Mar 2011]

RBAK links:

RBAK-RBAKDN (HGNC:):

RBAK-RBAKDN links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.13699558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RBAK	NM_021163.4 linkuse as main transcript	c.716G>A	p.Gly239Glu	missense_variant	5/5	ENST00000396912.2
RBAK-RBAKDN	NM_001204513.3 linkuse as main transcript	c.238+6393G>A		intron_variant
RBAK	NM_001204456.2 linkuse as main transcript	c.716G>A	p.Gly239Glu	missense_variant	6/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBAK	ENST00000396912.2 linkuse as main transcript	c.716G>A	p.Gly239Glu	missense_variant	5/5	1	NM_021163.4	P1	Q9NYW8-1
RBAK	ENST00000353796.7 linkuse as main transcript	c.716G>A	p.Gly239Glu	missense_variant	6/6	2		P1	Q9NYW8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461608

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727102

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:

8.99e-7

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

Jul 20, 2022

The c.716G>A (p.G239E) alteration is located in exon 5 (coding exon 4) of the RBAK gene. This alteration results from a G to A substitution at nucleotide position 716, causing the glycine (G) at amino acid position 239 to be replaced by a glutamic acid (E). 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

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.19

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.0071

M_CAP

Benign

0.0029

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

L;L

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.087

Sift

Benign

0.27

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.033

B;B

Vest4

0.12

MutPred

0.67

Gain of disorder (P = 0.0694);Gain of disorder (P = 0.0694);

MVP

0.11

MPC

0.093

ClinPred

0.089

GERP RS

1.7

Varity_R

0.18

gMVP

0.083

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