Genetic Variant ENST00000407184.5:c.395G>T (chr7-5072457-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The ENST00000407184.5(RBAK-RBAKDN):c.395G>T(p.Arg132Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,389,886 control chromosomes in the GnomAD database, with no homozygous occurrence. 6/9 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. R132Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

RBAK-RBAKDN
ENST00000407184.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.425

Variant links:

Genes affected

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:

RBAKDN (HGNC:33770): (RBAK downstream neighbor)

RBAKDN links:

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ACMG classification

Classification made for transcript

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-RBAKDN	NM_001204513.3 link	c.334G>T	p.Gly112*	stop_gained	Exon 5 of 6		NP_001191442.1	A0A0A6YYG8
RBAKDN	NR_015343.2 link	n.237G>T		non_coding_transcript_exon_variant	Exon 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	Protein	UniProt
RBAK-RBAKDN	ENST00000407184.5 link	c.395G>T	p.Arg132Leu	missense_variant	Exon 7 of 8	2	ENSP00000385560.1	I3L0D1
RBAKDN	ENST00000498308.1 link	n.172G>T		non_coding_transcript_exon_variant	Exon 2 of 3	1	ENSP00000520911.1
RBAK-RBAKDN	ENST00000396904.2 link	c.334G>T	p.Gly112*	stop_gained	Exon 5 of 6	4	ENSP00000380112.2	A0A0A6YYG8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.19e-7

AC:

AN:

1389886

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

685502

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.30e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Benign

-0.51

CADD

Benign

0.83

DANN

Benign

0.87

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.89

FATHMM_MKL

Benign

0.037

Vest4

0.012

ClinPred

0.30

GERP RS

-2.0

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over