Variant 11-89912041-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001384911.1(TRIM49D1):c.905G>A(p.Arg302Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 19)

Exomes 𝑓: 0.000016 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49D1
NM_001384911.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

TRIM49D1 (HGNC:43973): (tripartite motif containing 49D1) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

TRIM49D1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07147455).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49D1	NM_001384911.1 link	c.905G>A	p.Arg302Gln	missense_variant	8/8	ENST00000420869.3	NP_001371840.1
TRIM49D1	NM_001206627.2 link	c.905G>A	p.Arg302Gln	missense_variant	7/7		NP_001193556.1	C9J1S8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIM49D1	ENST00000420869.3 link	c.905G>A	p.Arg302Gln	missense_variant	8/8	5	NM_001384911.1	ENSP00000474678.1	C9J1S8
TRIM49D1	ENST00000605881.5 link	c.674G>A	p.Arg225Gln	missense_variant	6/6	1		ENSP00000479562.1	A0A087WVN7
TRIM49D1	ENST00000530311.6 link	c.905G>A	p.Arg302Gln	missense_variant	8/8	5		ENSP00000474850.1	C9J1S8

Frequencies

GnomAD3 genomes

AF:

0.0000597

AC:

AN:

134042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000136

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000756

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000216

Gnomad SAS

AF:

0.000238

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000403

AC:

AN:

49576

Hom.:

AF XY:

0.0000670

AC XY:

AN XY:

29836

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000293

Gnomad EAS exome

AF:

0.000435

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000161

AC:

AN:

1116752

Hom.:

Cov.:

AF XY:

0.0000219

AC XY:

AN XY:

547550

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000141

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000376

Gnomad4 NFE exome

AF:

0.0000142

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000597

AC:

AN:

134086

Hom.:

Cov.:

AF XY:

0.0000777

AC XY:

AN XY:

64334

show subpopulations

Gnomad4 AFR

AF:

0.000136

Gnomad4 AMR

AF:

0.0000755

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000217

Gnomad4 SAS

AF:

0.000239

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000843

Hom.:

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

Oct 02, 2023

The c.905G>A (p.R302Q) alteration is located in exon 6 (coding exon 6) of the TRIM49D1 gene. This alteration results from a G to A substitution at nucleotide position 905, causing the arginine (R) at amino acid position 302 to be replaced by a glutamine (Q). 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

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Benign

-0.32

CADD

Benign

7.0

DANN

Benign

0.60

DEOGEN2

Benign

0.0053

T;.;T

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.40

.;T;.

M_CAP

Benign

0.0077

MetaRNN

Benign

0.071

T;T;T

PrimateAI

Benign

0.42

Sift4G

Benign

0.13

T;T;T

Polyphen

0.0030

B;.;B

Vest4

0.079

MVP

0.25

GERP RS

-3.6

Varity_R

0.027

gMVP

0.023

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