NM_021163.4:c.246G>A

Variant names:

• chr7-5063702-G-A
• rs760493837
• NM_021163.4:c.246G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_021163.4(RBAK):​c.246G>A​(p.Trp82*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RBAK	NM_021163.4	c.246G>A	p.Trp82*	stop_gained	Exon 5 of 5	ENST00000396912.2	NP_066986.1
RBAK	NM_001204456.2	c.246G>A	p.Trp82*	stop_gained	Exon 6 of 6		NP_001191385.1
RBAK-RBAKDN	NM_001204513.3	c.238+5923G>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.246G>A	p.Trp82*	stop_gained	Exon 5 of 5	1	NM_021163.4	ENSP00000380120.1
RBAK-RBAKDN	ENST00000407184.5	c.246G>A	p.Trp82*	stop_gained	Exon 6 of 8	2		ENSP00000385560.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000423 AC: 1 AN: 236456 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 128216

Gnomad AFR exome AF: 0.0000631

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Uncertain	0.010
CADD	Pathogenic	34
DANN	Uncertain	0.98
Eigen	Benign	0.037
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.00014	N
Vest4		0.26
GERP RS		1.4

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs760493837; hg19: chr7-5103333;