7-5063804-T-A

Variant names:

• chr7-5063804-T-A
• NM_021163.4:c.348T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021163.4(RBAK):​c.348T>A​(p.Asn116Lys) 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. 14/20 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: not found (cov: 33)
• Consequence: RBAK NM_021163.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.600

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 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=0.05797082).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBAK	NM_021163.4	c.348T>A	p.Asn116Lys	missense_variant	Exon 5 of 5	ENST00000396912.2	NP_066986.1
RBAK	NM_001204456.2	c.348T>A	p.Asn116Lys	missense_variant	Exon 6 of 6		NP_001191385.1
RBAK-RBAKDN	NM_001204513.3	c.238+6025T>A		intron_variant	Intron 4 of 5		NP_001191442.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RBAK	ENST00000396912.2	c.348T>A	p.Asn116Lys	missense_variant	Exon 5 of 5	1	NM_021163.4	ENSP00000380120.1
RBAK-RBAKDN	ENST00000407184.5	c.299+49T>A		intron_variant	Intron 6 of 7	2		ENSP00000385560.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 05, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.348T>A (p.N116K) alteration is located in exon 5 (coding exon 4) of the RBAK gene. This alteration results from a T to A substitution at nucleotide position 348, causing the asparagine (N) at amino acid position 116 to be replaced by a lysine (K). 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	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.9
DANN	Benign	0.17
DEOGEN2	Benign	0.052	T;T
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.94
FATHMM_MKL	Benign	0.00030	N
LIST_S2	Benign	0.27	.;T
M_CAP	Benign	0.0016	T
MetaRNN	Benign	0.058	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.12	N;N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.030
Sift	Benign	0.20	T;T
Sift4G	Benign	0.29	T;T
Polyphen		0.18	B;B
Vest4		0.057
MutPred		0.44		Gain of ubiquitination at N116 (P = 0.0054);Gain of ubiquitination at N116 (P = 0.0054);
MVP		0.085
MPC		0.083
ClinPred		0.059	T
GERP RS		2.2
Varity_R		0.056
gMVP		0.14

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: chr7-5103435;