Variant 2-7039638-A-G 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_014746.6(RNF144A):c.757A>G(p.Ile253Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,612,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000038 ( 0 hom. )

Consequence

RNF144A
NM_014746.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.63

Variant links:

Genes affected

RNF144A (HGNC:20457): (ring finger protein 144A) This gene encodes a member of a family of RING finger domain-containing E3 ubiquitin ligases that also includes parkin and parc. The expression of this gene is induced by DNA damage. The encoded protein interacts with the cytoplasmic DNA-dependent protein kinase, catalytic subunit (DNA-PKcs) and promotes its degradation through ubiquitination. The orthologous mouse protein has been shown to interact with a ubiquitin-conjugating enzyme involved in embryonic development. [provided by RefSeq, Mar 2017]

RNF144A 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=0.08134243).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF144A	NM_014746.6 linkuse as main transcript	c.757A>G	p.Ile253Val	missense_variant	9/9	ENST00000320892.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RNF144A	ENST00000320892.11 linkuse as main transcript	c.757A>G	p.Ile253Val	missense_variant	9/9	1	NM_014746.6	P1
RNF144A	ENST00000432850.1 linkuse as main transcript	c.734+9423A>G		intron_variant		3
RNF144A	ENST00000467276.5 linkuse as main transcript	n.878A>G		non_coding_transcript_exon_variant	6/6	3

Frequencies

GnomAD3 genomes

AF:

0.0000598

AC:

AN:

150578

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00145

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000216

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000297

Gnomad OTH

AF:

0.000484

GnomAD3 exomes

AF:

0.0000677

AC:

AN:

251072

Hom.:

AF XY:

0.0000663

AC XY:

AN XY:

135718

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000895

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000376

AC:

AN:

1461436

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727056

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000842

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000104

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000153

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.0000598

AC:

AN:

150578

Hom.:

Cov.:

AF XY:

0.0000817

AC XY:

AN XY:

73478

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00145

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000216

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000297

Gnomad4 OTH

AF:

0.000484

Alfa

AF:

0.000135

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

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

Jun 24, 2022

The c.757A>G (p.I253V) alteration is located in exon 9 (coding exon 7) of the RNF144A gene. This alteration results from a A to G substitution at nucleotide position 757, causing the isoleucine (I) at amino acid position 253 to be replaced by a valine (V). 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

Pathogenic

0.78

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.38

Cadd

Uncertain

Dann

Uncertain

1.0

DEOGEN2

Benign

0.034

Eigen

Benign

-0.0042

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.012

MetaRNN

Benign

0.081

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.73

REVEL

Benign

0.16

Sift

Benign

0.19

Sift4G

Benign

0.29

Polyphen

0.064

Vest4

0.47

MutPred

0.35

Gain of sheet (P = 0.0028);

MVP

0.22

MPC

0.58

ClinPred

0.16

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.14

gMVP

0.50

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