Variant 11-89798548-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The ENST00000329758.5(TRIM49):c.941A>C(p.Asp314Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000638 in 1,566,696 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000023 ( 0 hom., cov: 21)

Exomes 𝑓: 0.000067 ( 5 hom. )

Consequence

TRIM49
ENST00000329758.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.827

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.25848216).

BS2

High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49	NM_020358.2 linkuse as main transcript	c.941A>C	p.Asp314Ala	missense_variant	8/8	ENST00000329758.5	NP_065091.1	P0CI25
TRIM49	XM_017018027.3 linkuse as main transcript	c.710A>C	p.Asp237Ala	missense_variant	5/5		XP_016873516.1	E9PK69
TRIM49	XM_024448617.2 linkuse as main transcript	c.738+3154A>C		intron_variant			XP_024304385.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM49	ENST00000329758.5 linkuse as main transcript	c.941A>C	p.Asp314Ala	missense_variant	8/8	1	NM_020358.2	ENSP00000327604.1		P0CI25
TRIM49	ENST00000532501.2 linkuse as main transcript	c.710A>C	p.Asp237Ala	missense_variant	6/6	5		ENSP00000431618.2		E9PK69

Frequencies

GnomAD3 genomes

AF:

0.0000233

AC:

AN:

128762

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:

0.0000467

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000291

AC:

AN:

240826

Hom.:

AF XY:

0.0000382

AC XY:

AN XY:

130898

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:

0.0000632

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000675

AC:

AN:

1437934

Hom.:

Cov.:

AF XY:

0.0000489

AC XY:

AN XY:

715622

show subpopulations

Gnomad4 AFR exome

AF:

0.0000323

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:

0.0000827

Gnomad4 OTH exome

AF:

0.0000844

GnomAD4 genome

AF:

0.0000233

AC:

AN:

128762

Hom.:

Cov.:

AF XY:

0.0000321

AC XY:

AN XY:

62250

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000467

Gnomad4 OTH

AF:

0.00

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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 15, 2024

The c.941A>C (p.D314A) alteration is located in exon 8 (coding exon 6) of the TRIM49 gene. This alteration results from a A to C substitution at nucleotide position 941, causing the aspartic acid (D) at amino acid position 314 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

0.12

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.060

T;.

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.41

T;T

M_CAP

Benign

0.0014

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Benign

0.036

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.043

D;D

Polyphen

0.97

D;.

Vest4

0.11

MutPred

0.69

Gain of catalytic residue at G312 (P = 0.1253);.;

MVP

0.043

MPC

1.5

ClinPred

0.23

GERP RS

0.82

Varity_R

0.13

gMVP

0.047

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