Genetic Variant NM_020358.2:c.1321C>T (chr11-89798168-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_020358.2(TRIM49):c.1321C>T(p.Pro441Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000193 in 1,399,390 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000011 ( 0 hom., cov: 11)

Exomes 𝑓: 0.000019 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49
NM_020358.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0140

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03178808).

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.1321C>T	p.Pro441Ser	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.1321C>T	p.Pro441Ser	missense	Exon 8 of 8	ENSP00000327604.1	P0CI25
	TRIM49	ENST00000532501.2	TSL:5	c.1090C>T	p.Pro364Ser	missense	Exon 6 of 6	ENSP00000431618.2	E9PK69

Frequencies

GnomAD3 genomes

AF:

0.0000111

AC:

AN:

90216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000208

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000170

AC:

AN:

176850

AF XY:

0.0000310

show subpopulations

Gnomad AFR exome

AF:

0.000104

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:

0.0000254

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000193

AC:

AN:

1399390

Hom.:

Cov.:

AF XY:

0.0000202

AC XY:

AN XY:

694026

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29912

American (AMR)

AF:

0.00

AC:

AN:

38496

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24904

East Asian (EAS)

AF:

0.00

AC:

AN:

35778

South Asian (SAS)

AF:

0.00

AC:

AN:

82940

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4686

European-Non Finnish (NFE)

AF:

0.0000242

AC:

AN:

1075308

Other (OTH)

AF:

0.0000173

AC:

AN:

57808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

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

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000111

AC:

AN:

90216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

42146

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19426

American (AMR)

AF:

0.00

AC:

AN:

7614

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2594

East Asian (EAS)

AF:

0.00

AC:

AN:

2740

South Asian (SAS)

AF:

0.00

AC:

AN:

2436

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

250

European-Non Finnish (NFE)

AF:

0.0000208

AC:

AN:

48090

Other (OTH)

AF:

0.00

AC:

AN:

1168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000262

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

Benign

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.54

CADD

Benign

3.3

(source)

DANN

Benign

0.34

DEOGEN2

Benign

0.0019

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00060

LIST_S2

Benign

0.42

M_CAP

Benign

0.0051

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

PhyloP100

-0.014

PrimateAI

Benign

0.40

PROVEAN

Benign

0.24

REVEL

Benign

0.035

Sift

Benign

0.30

Sift4G

Benign

0.59

Polyphen

0.045

Vest4

0.063

MVP

0.068

MPC

1.2

ClinPred

0.020

GERP RS

-2.4

Varity_R

0.030

gMVP

0.032

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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