7-5063893-CT-GC

Variant names:

• chr7-5063893-CT-GC
• NM_021163.4:c.437_438delCTinsGC
• RBAK p.Ser146Cys

Variant summary

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

The NM_021163.4(RBAK):​c.437_438delCTinsGC​(p.Ser146Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RBAK NM_021163.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.22
• Publications: 0 publications found

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

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

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBAK	NM_021163.4	MANE Select	c.437_438delCTinsGC	p.Ser146Cys	missense	N/A	NP_066986.1	Q9NYW8-1
	RBAK	NM_001204456.2		c.437_438delCTinsGC	p.Ser146Cys	missense	N/A	NP_001191385.1	Q9NYW8-1
	RBAK-RBAKDN	NM_001204513.3		c.238+6114_238+6115delCTinsGC		intron	N/A	NP_001191442.1	A0A0A6YYG8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RBAK	ENST00000396912.2	TSL:1 MANE Select	c.437_438delCTinsGC	p.Ser146Cys	missense	N/A	ENSP00000380120.1	Q9NYW8-1
	RBAK-RBAKDN	ENST00000407184.5	TSL:2	c.299+138_299+139delCTinsGC		intron	N/A	ENSP00000385560.1	I3L0D1
	RBAK	ENST00000353796.7	TSL:2	c.437_438delCTinsGC	p.Ser146Cys	missense	N/A	ENSP00000275423.4	Q9NYW8-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-1.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-5103524;