Variant 2-7024394-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014746.6(RNF144A):c.535G>A(p.Asp179Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000909 in 1,609,278 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00092 ( 1 hom. )

Consequence

RNF144A
NM_014746.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.83

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.011024326).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNF144A	NM_014746.6 linkuse as main transcript	c.535G>A	p.Asp179Asn	missense_variant	7/9	ENST00000320892.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
RNF144A	ENST00000320892.11 linkuse as main transcript	c.535G>A	p.Asp179Asn	missense_variant	7/9	1	NM_014746.6	P1
RNF144A	ENST00000432850.1 linkuse as main transcript	c.523G>A	p.Asp175Asn	missense_variant	5/7	3
RNF144A	ENST00000467276.5 linkuse as main transcript	n.656G>A		non_coding_transcript_exon_variant	4/6	3
RNF144A	ENST00000480970.1 linkuse as main transcript	n.581G>A		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes

AF:

0.000795

AC:

121

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.0132

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00519

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00115

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.000653

AC:

164

AN:

251296

Hom.:

AF XY:

0.000692

AC XY:

AN XY:

135816

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00377

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00100

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000921

AC:

1342

AN:

1457056

Hom.:

Cov.:

AF XY:

0.000880

AC XY:

637

AN XY:

723636

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00391

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00107

Gnomad4 OTH exome

AF:

0.000798

GnomAD4 genome

AF:

0.000795

AC:

121

AN:

152222

Hom.:

Cov.:

AF XY:

0.000699

AC XY:

AN XY:

74364

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00519

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00115

Gnomad4 OTH

AF:

0.000955

Alfa

AF:

0.000861

Hom.:

Bravo

AF:

0.000827

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000667

AC:

EpiCase

AF:

0.00120

EpiControl

AF:

0.00119

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 03, 2021

The c.535G>A (p.D179N) alteration is located in exon 7 (coding exon 5) of the RNF144A gene. This alteration results from a G to A substitution at nucleotide position 535, causing the aspartic acid (D) at amino acid position 179 to be replaced by an asparagine (N). 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

0.097

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.31

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.048

MetaRNN

Benign

0.011

MetaSVM

Benign

-0.93

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

0.88

REVEL

Uncertain

0.38

Sift

Benign

0.46

Sift4G

Benign

0.74

Polyphen

0.64

Vest4

0.43

MVP

0.34

MPC

0.44

ClinPred

0.037

GERP RS

5.9

Varity_R

0.079

gMVP

0.20

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