Genetic Variant NM_021163.4:c.983A>G (chr7-5064439-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021163.4(RBAK):c.983A>G(p.Gln328Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 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)

Consequence

RBAK
NM_021163.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.290

Publications

0 publications found

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:42971): (RBAK-RBAKDN readthrough) This locus represents naturally occurring read-through transcription between the neighboring RBAK (RB-associated KRAB zinc finger) and LOC389458 (hypothetical LOC389458) genes on chromosome 7. The read-through transcript encodes a protein that shares sequence identity with the upstream gene product but its C-terminal region is distinct due to frameshifts relative to the downstream gene. [provided by RefSeq, Mar 2011]

RBAK-RBAKDN links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14744687).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021163.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBAK	NM_021163.4	MANE Select	c.983A>G	p.Gln328Arg	missense	Exon 5 of 5	NP_066986.1	Q9NYW8-1
RBAK	NM_001204456.2		c.983A>G	p.Gln328Arg	missense	Exon 6 of 6	NP_001191385.1	Q9NYW8-1
RBAK-RBAKDN	NM_001204513.3		c.238+6660A>G		intron	N/A	NP_001191442.1	A0A0A6YYG8

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RBAK	ENST00000396912.2	TSL:1 MANE Select	c.983A>G	p.Gln328Arg	missense	Exon 5 of 5	ENSP00000380120.1	Q9NYW8-1
RBAK-RBAKDN	ENST00000407184.5	TSL:2	c.299+684A>G		intron	N/A	ENSP00000385560.1	I3L0D1
RBAK	ENST00000353796.7	TSL:2	c.983A>G	p.Gln328Arg	missense	Exon 6 of 6	ENSP00000275423.4	Q9NYW8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

Eigen

Benign

-0.010

Eigen_PC

Benign

-0.063

FATHMM_MKL

Benign

0.0020

LIST_S2

Benign

0.26

M_CAP

Benign

0.0043

MetaRNN

Benign

0.15

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.17

PhyloP100

0.29

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-1.3

REVEL

Benign

0.11

Sift

Benign

0.48

Sift4G

Benign

0.41

Polyphen

0.99

Vest4

0.13

MutPred

0.37

Gain of MoRF binding (P = 0.018)

MVP

0.11

MPC

0.43

ClinPred

0.79

GERP RS

3.6

Varity_R

0.16

gMVP

0.10

Mutation Taster

=76/24

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over