Variant 2-6997026-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_014746.6(RNF144A):c.100A>G(p.Thr34Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,864 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: not found (cov: 33)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

RNF144A
NM_014746.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.83

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32091594).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNF144A	NM_014746.6 linkuse as main transcript	c.100A>G	p.Thr34Ala	missense_variant	3/9	ENST00000320892.11	NP_055561.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNF144A	ENST00000320892.11 linkuse as main transcript	c.100A>G	p.Thr34Ala	missense_variant	3/9	1	NM_014746.6	ENSP00000321330	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251458

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135896

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727236

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:

0.00000630

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000611

Hom.:

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

Jul 06, 2021

The c.100A>G (p.T34A) alteration is located in exon 3 (coding exon 1) of the RNF144A gene. This alteration results from a A to G substitution at nucleotide position 100, causing the threonine (T) at amino acid position 34 to be replaced by an alanine (A). 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

0.072

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

T;.;.

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

T;.;T

M_CAP

Benign

0.043

MetaRNN

Benign

0.32

T;T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.2

L;.;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.69

PROVEAN

Benign

-0.76

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.52

T;D;D

Sift4G

Benign

0.77

T;T;T

Polyphen

0.96

P;.;.

Vest4

0.65

MVP

0.21

MPC

0.48

ClinPred

0.58

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.52

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