Genetic Variant TRIM49D2:p.Arg315His (chr11-89932470-G-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001105522.1(TRIM49D2):c.944G>A(p.Arg315His) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000056 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49D2
NM_001105522.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -5.32

Publications

0 publications found

Variant links:

Genes affected

TRIM49D2 (HGNC:37217): (tripartite motif containing 49D2) 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]

TRIM49D2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.052407235).

BP6

Variant 11-89932470-G-A is Benign according to our data. Variant chr11-89932470-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3182553.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105522.1. 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
	TRIM49D2	NM_001105522.1	MANE Select	c.944G>A	p.Arg315His	missense	Exon 7 of 7	NP_001098992.1	C9J1S8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM49D2	ENST00000623787.3	TSL:5 MANE Select	c.944G>A	p.Arg315His	missense	Exon 7 of 7	ENSP00000485097.1	C9J1S8
	TRIM49D2	ENST00000526396.3	TSL:5	c.944G>A	p.Arg315His	missense	Exon 6 of 6	ENSP00000485325.1	C9J1S8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

22642

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000144

AC:

AN:

6936

AF XY:

0.00

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:

0.000292

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000565

AC:

AN:

247906

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

123152

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

1568

American (AMR)

AF:

0.00

AC:

AN:

2974

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4336

East Asian (EAS)

AF:

0.000251

AC:

AN:

7980

South Asian (SAS)

AF:

0.00

AC:

AN:

7572

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6132

Middle Eastern (MID)

AF:

0.00

AC:

AN:

762

European-Non Finnish (NFE)

AF:

0.0000582

AC:

AN:

206220

Other (OTH)

AF:

0.00

AC:

AN:

10362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

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: AC0;AS_VQSR

AF:

0.00

AC:

AN:

22642

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

10728

African (AFR)

AF:

0.00

AC:

AN:

2210

American (AMR)

AF:

0.00

AC:

AN:

1894

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

790

East Asian (EAS)

AF:

0.00

AC:

AN:

972

South Asian (SAS)

AF:

0.00

AC:

AN:

602

European-Finnish (FIN)

AF:

0.00

AC:

AN:

1622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

14060

Other (OTH)

AF:

0.00

AC:

AN:

318

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.070

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

0.34

(source)

DANN

Benign

0.77

FATHMM_MKL

Benign

0.00055

LIST_S2

Benign

0.63

MetaRNN

Benign

0.052

PhyloP100

-5.3

PrimateAI

Uncertain

0.52

Sift4G

Benign

0.25

Vest4

0.10

MVP

0.014

GERP RS

-1.8

gMVP

0.016

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

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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