Variant 6-18459720-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_182757.4(RNF144B):c.650C>T(p.Thr217Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000491 in 1,613,992 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00037 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00050 ( 2 hom. )

Consequence

RNF144B
NM_182757.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.83

Variant links:

Genes affected

RNF144B (HGNC:21578): (ring finger protein 144B) Enables ubiquitin-protein transferase activity. Involved in negative regulation of apoptotic process and ubiquitin-dependent protein catabolic process. Located in mitochondrial membrane. [provided by Alliance of Genome Resources, Apr 2022]

RNF144B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF144B	NM_182757.4 linkuse as main transcript	c.650C>T	p.Thr217Ile	missense_variant	6/8	ENST00000259939.4
RNF144B	XM_047418594.1 linkuse as main transcript	c.545C>T	p.Thr182Ile	missense_variant	4/6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF144B	ENST00000259939.4 linkuse as main transcript	c.650C>T	p.Thr217Ile	missense_variant	6/8	1	NM_182757.4	P1	Q7Z419-1

Frequencies

GnomAD3 genomes

AF:

0.000375

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000632

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000286

AC:

AN:

251338

Hom.:

AF XY:

0.000280

AC XY:

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.000572

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000503

AC:

736

AN:

1461790

Hom.:

Cov.:

AF XY:

0.000495

AC XY:

360

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.000636

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

AF:

0.000375

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000363

AC XY:

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000847

Gnomad4 NFE

AF:

0.000632

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000528

Hom.:

Bravo

AF:

0.000268

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000698

AC:

ExAC

AF:

0.000222

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000178

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 01, 2022

The c.650C>T (p.T217I) alteration is located in exon 6 (coding exon 5) of the RNF144B gene. This alteration results from a C to T substitution at nucleotide position 650, causing the threonine (T) at amino acid position 217 to be replaced by an isoleucine (I). 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

Uncertain

0.46

BayesDel_addAF

Benign

-0.060

BayesDel_noAF

Uncertain

0.070

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Benign

0.24

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.040

MetaRNN

Uncertain

0.62

MetaSVM

Benign

-0.52

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.92

PROVEAN

Benign

0.55

REVEL

Uncertain

0.50

Sift

Benign

0.23

Sift4G

Benign

0.21

Polyphen

0.77

Vest4

0.76

MVP

0.91

MPC

0.13

ClinPred

0.096

GERP RS

6.1

Varity_R

0.20

gMVP

0.55

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

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