7-5064439-A-G

Position:

• chr7-5064439-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBAK NM_021163.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.290

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-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]

ACMG classification

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=0.14744687).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBAK	NM_021163.4	c.983A>G	p.Gln328Arg	missense_variant	5/5	ENST00000396912.2	NP_066986.1
RBAK	NM_001204456.2	c.983A>G	p.Gln328Arg	missense_variant	6/6		NP_001191385.1
RBAK-RBAKDN	NM_001204513.3	c.238+6660A>G		intron_variant			NP_001191442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RBAK	ENST00000396912.2	c.983A>G	p.Gln328Arg	missense_variant	5/5	1	NM_021163.4	ENSP00000380120.1
RBAK-RBAKDN	ENST00000407184.5	c.299+684A>G		intron_variant		2		ENSP00000385560.1
RBAK	ENST00000353796.7	c.983A>G	p.Gln328Arg	missense_variant	6/6	2		ENSP00000275423.4
RBAK-RBAKDN	ENST00000396904.2	c.238+6660A>G		intron_variant		4		ENSP00000380112.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 14, 2024

The c.983A>G (p.Q328R) alteration is located in exon 5 (coding exon 4) of the RBAK gene. This alteration results from a A to G substitution at nucleotide position 983, causing the glutamine (Q) at amino acid position 328 to be replaced by an arginine (R). 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	Pathogenic	0.89
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.055	T;T
Eigen	Benign	-0.010
Eigen_PC	Benign	-0.063
FATHMM_MKL	Benign	0.0020	N
LIST_S2	Benign	0.26	.;T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.17	N;N
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.3	N;N
REVEL	Benign	0.11
Sift	Benign	0.48	T;T
Sift4G	Benign	0.41	T;T
Polyphen		0.99	D;D
Vest4		0.13
MutPred		0.37		Gain of MoRF binding (P = 0.018);Gain of MoRF binding (P = 0.018);
MVP		0.11
MPC		0.43
ClinPred		0.79	D
GERP RS		3.6
Varity_R		0.16
gMVP		0.10

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.

Other links and lift over

hg19: chr7-5104070;