Genetic Variant NM_001199383.2:c.1958C>G (chr5-159158704-G-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001199383.2(RNF145):c.1958C>G(p.Ala653Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A653V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RNF145
NM_001199383.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.373

Publications

0 publications found

Variant links:

Genes affected

RNF145 (HGNC:20853): (ring finger protein 145) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in protein ubiquitination. Predicted to be located in endoplasmic reticulum membrane. Predicted to be integral component of membrane. Predicted to be active in endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]

RNF145 links:

LINC02202 (HGNC:53068): (long intergenic non-protein coding RNA 2202)

LINC02202 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06943685).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001199383.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF145	NM_001199383.2	MANE Select	c.1958C>G	p.Ala653Gly	missense	Exon 11 of 11	NP_001186312.1	Q96MT1-1
RNF145	NM_001199380.2		c.2048C>G	p.Ala683Gly	missense	Exon 11 of 11	NP_001186309.1	Q96MT1-5
RNF145	NM_144726.3		c.2042C>G	p.Ala681Gly	missense	Exon 11 of 11	NP_653327.1	Q96MT1-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RNF145	ENST00000424310.7	TSL:1 MANE Select	c.1958C>G	p.Ala653Gly	missense	Exon 11 of 11	ENSP00000409064.2	Q96MT1-1
RNF145	ENST00000518802.5	TSL:1	c.2048C>G	p.Ala683Gly	missense	Exon 11 of 11	ENSP00000430955.1	Q96MT1-5
RNF145	ENST00000274542.6	TSL:2	c.2042C>G	p.Ala681Gly	missense	Exon 11 of 11	ENSP00000274542.2	Q96MT1-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461622

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111814

Other (OTH)

AF:

0.00

AC:

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

3.3

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.021

Eigen

Benign

-0.89

Eigen_PC

Benign

-0.87

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.74

M_CAP

Benign

0.063

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.87

MutationAssessor

Benign

0.34

PhyloP100

0.37

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.24

REVEL

Benign

0.18

Sift

Benign

0.19

Sift4G

Benign

0.35

Polyphen

0.095

Vest4

0.065

MutPred

0.12

Loss of helix (P = 0.079)

MVP

0.35

MPC

0.023

ClinPred

0.087

GERP RS

3.3

Varity_R

0.029

gMVP

0.11

Mutation Taster

=96/4

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over