Variant 7-5072379-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001204513.3(RBAK-RBAKDN):c.256C>T(p.His86Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000457 in 1,533,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

RBAK-RBAKDN
NM_001204513.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.104

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:

RBAKDN (HGNC:):

RBAKDN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.07464704).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RBAK-RBAKDN	NM_001204513.3 linkuse as main transcript	c.256C>T	p.His86Tyr	missense_variant	5/6		NP_001191442.1	A0A0A6YYG8
RBAKDN	NR_015343.2 linkuse as main transcript	n.159C>T		non_coding_transcript_exon_variant	2/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
RBAK-RBAKDN	ENST00000407184.5 linkuse as main transcript	c.317C>T	p.Pro106Leu	missense_variant	7/8	2	ENSP00000385560.1	I3L0D1
RBAKDN	ENST00000498308.1 linkuse as main transcript	n.94C>T		non_coding_transcript_exon_variant	2/3	1	ENSP00000520911.1
RBAK-RBAKDN	ENST00000396904.2 linkuse as main transcript	c.256C>T	p.His86Tyr	missense_variant	5/6	4	ENSP00000380112.2	A0A0A6YYG8

Frequencies

GnomAD3 genomes

AF:

0.000138

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000434

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000227

AC:

AN:

132448

Hom.:

AF XY:

0.0000141

AC XY:

AN XY:

71172

show subpopulations

Gnomad AFR exome

AF:

0.000151

Gnomad AMR exome

AF:

0.0000469

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:

0.0000205

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000355

AC:

AN:

1381054

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

680582

show subpopulations

Gnomad4 AFR exome

AF:

0.000528

Gnomad4 AMR exome

AF:

0.0000613

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:

0.0000243

Gnomad4 OTH exome

AF:

0.0000875

GnomAD4 genome

AF:

0.000138

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.000434

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000856

Hom.:

Bravo

AF:

0.0000982

ExAC

AF:

0.0000137

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2021

The c.256C>T (p.H86Y) alteration is located in exon 5 (coding exon 4) of the RBAK-RBAKDN gene. This alteration results from a C to T substitution at nucleotide position 256, causing the histidine (H) at amino acid position 86 to be replaced by a tyrosine (Y). 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

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.65

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.23

LIST_S2

Benign

0.20

M_CAP

Benign

0.060

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.82

PROVEAN

Benign

-1.2

REVEL

Benign

0.066

Sift

Benign

0.091

Sift4G

Benign

0.13

Vest4

0.24

MutPred

0.38

Gain of loop (P = 0.0097);

MVP

0.043

MPC

0.27

ClinPred

0.18

GERP RS

3.2

gMVP

0.038

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over