Genetic Variant NM_021163.4:c.631A>G (chr7-5064087-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_021163.4(RBAK):c.631A>G(p.Met211Val) 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. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M211L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Consequence

RBAK
NM_021163.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.24

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0677174).

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.631A>G	p.Met211Val	missense	Exon 5 of 5	NP_066986.1	Q9NYW8-1
RBAK	NM_001204456.2		c.631A>G	p.Met211Val	missense	Exon 6 of 6	NP_001191385.1	Q9NYW8-1
RBAK-RBAKDN	NM_001204513.3		c.238+6308A>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.631A>G	p.Met211Val	missense	Exon 5 of 5	ENSP00000380120.1	Q9NYW8-1
RBAK-RBAKDN	ENST00000407184.5	TSL:2	c.299+332A>G		intron	N/A	ENSP00000385560.1	I3L0D1
RBAK	ENST00000353796.7	TSL:2	c.631A>G	p.Met211Val	missense	Exon 6 of 6	ENSP00000275423.4	Q9NYW8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249618

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

4.4

(source)

DANN

Benign

0.44

DEOGEN2

Benign

0.026

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00041

LIST_S2

Benign

0.0064

M_CAP

Benign

0.0030

MetaRNN

Benign

0.068

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.32

PhyloP100

1.2

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.76

REVEL

Benign

0.072

Sift

Benign

0.23

Sift4G

Uncertain

0.025

Polyphen

0.0040

Vest4

0.11

MutPred

0.66

Gain of helix (P = 0.1736)

MVP

0.055

MPC

0.072

ClinPred

0.016

GERP RS

-0.55

Varity_R

0.040

gMVP

0.17

Mutation Taster

=92/8

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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