Genetic Variant TRIM49:p.Ala330Pro (chr11-89798501-C-G) – 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_020358.2(TRIM49):c.988G>C(p.Ala330Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000481 in 1,454,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

TRIM49
NM_020358.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.39

Publications

0 publications found

Variant links:

Genes affected

TRIM49 (HGNC:13431): (tripartite motif containing 49) The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. This gene has been found to be preferentially expressed in testis. Related pseudogenes and gene duplicates have also been identified on chromosome 11. [provided by RefSeq, Aug 2010]

TRIM49 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=0.18700737).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020358.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM49	NM_020358.2	MANE Select	c.988G>C	p.Ala330Pro	missense	Exon 8 of 8	NP_065091.1	P0CI25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM49	ENST00000329758.5	TSL:1 MANE Select	c.988G>C	p.Ala330Pro	missense	Exon 8 of 8	ENSP00000327604.1	P0CI25
	TRIM49	ENST00000532501.2	TSL:5	c.757G>C	p.Ala253Pro	missense	Exon 6 of 6	ENSP00000431618.2	E9PK69

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000124

AC:

AN:

241106

AF XY:

0.00000761

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000182

Gnomad OTH exome

AF:

0.000169

GnomAD4 exome

AF:

0.00000481

AC:

AN:

1454952

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724062

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32350

American (AMR)

AF:

0.00

AC:

AN:

44430

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26078

East Asian (EAS)

AF:

0.00

AC:

AN:

39004

South Asian (SAS)

AF:

0.00

AC:

AN:

86022

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53184

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00000541

AC:

AN:

1108130

Other (OTH)

AF:

0.00

AC:

AN:

60054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

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.:

ExAC

AF:

0.0000166

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.11

Eigen

Benign

-0.68

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.41

M_CAP

Benign

0.0046

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.7

PhyloP100

-2.4

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.26

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.017

Polyphen

0.98

Vest4

0.25

MutPred

0.62

Loss of catalytic residue at A330 (P = 0.0024)

MVP

0.11

MPC

2.1

ClinPred

0.21

GERP RS

-2.1

Varity_R

0.27

gMVP

0.24

Mutation Taster

=98/2

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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