Variant 6-18427636-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_182757.4(RNF144B):c.221C>T(p.Thr74Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,480 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

RNF144B
NM_182757.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.86

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.772

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF144B	NM_182757.4 linkuse as main transcript	c.221C>T	p.Thr74Ile	missense_variant	3/8	ENST00000259939.4
RNF144B	XM_047418594.1 linkuse as main transcript	c.166-12048C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNF144B	ENST00000259939.4 linkuse as main transcript	c.221C>T	p.Thr74Ile	missense_variant	3/8	1	NM_182757.4	P1	Q7Z419-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251110

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135706

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461480

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727032

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Apr 13, 2022

The c.221C>T (p.T74I) alteration is located in exon 3 (coding exon 2) of the RNF144B gene. This alteration results from a C to T substitution at nucleotide position 221, causing the threonine (T) at amino acid position 74 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

Benign

0.28

BayesDel_addAF

Benign

-0.028

BayesDel_noAF

Benign

-0.28

Cadd

Uncertain

Dann

Pathogenic

1.0

DEOGEN2

Benign

0.16

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.011

MetaRNN

Pathogenic

0.77

MetaSVM

Benign

-0.93

MutationAssessor

Uncertain

2.9

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.53

PROVEAN

Uncertain

-3.9

REVEL

Uncertain

0.31

Sift

Uncertain

0.013

Sift4G

Uncertain

0.011

Polyphen

0.99

Vest4

0.68

MutPred

0.53

Loss of catalytic residue at T74 (P = 0.0291);

MVP

0.75

MPC

0.21

ClinPred

0.93

GERP RS

5.7

Varity_R

0.33

gMVP

0.67

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