Genetic Variant NM_020358.2:c.988G>C (chr11-89798501-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 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. 13/21 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

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.18700737).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM49	NM_020358.2 link	c.988G>C	p.Ala330Pro	missense_variant	Exon 8 of 8	ENST00000329758.5	NP_065091.1	P0CI25
TRIM49	XM_017018027.3 link	c.757G>C	p.Ala253Pro	missense_variant	Exon 5 of 5		XP_016873516.1	E9PK69
TRIM49	XM_024448617.2 link	c.738+3201G>C		intron_variant	Intron 3 of 5		XP_024304385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM49	ENST00000329758.5 link	c.988G>C	p.Ala330Pro	missense_variant	Exon 8 of 8	1	NM_020358.2	ENSP00000327604.1		P0CI25
TRIM49	ENST00000532501.2 link	c.757G>C	p.Ala253Pro	missense_variant	Exon 6 of 6	5		ENSP00000431618.2		E9PK69

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000124

AC:

AN:

241106

Hom.:

AF XY:

0.00000761

AC XY:

AN XY:

131354

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:

0.0000182

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

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:

0.0000188

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 04, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.988G>C (p.A330P) alteration is located in exon 8 (coding exon 6) of the TRIM49 gene. This alteration results from a G to C substitution at nucleotide position 988, causing the alanine (A) at amino acid position 330 to be replaced by a proline (P). 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

Uncertain

0.49

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.0046

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.7

M;.

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.5

N;N

REVEL

Benign

0.26

Sift

Uncertain

0.0080

D;D

Sift4G

Uncertain

0.017

D;D

Polyphen

0.98

D;.

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

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