Variant 11-89911723-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001384911.1(TRIM49D1):c.1223A>T(p.His408Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/12 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 13)

Exomes 𝑓: 0.00053 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

TRIM49D1
NM_001384911.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -3.75

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018754244).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49D1	NM_001384911.1 linkuse as main transcript	c.1223A>T	p.His408Leu	missense_variant	8/8	ENST00000420869.3	NP_001371840.1
TRIM49D1	NM_001206627.2 linkuse as main transcript	c.1223A>T	p.His408Leu	missense_variant	7/7		NP_001193556.1	C9J1S8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
TRIM49D1	ENST00000420869.3 linkuse as main transcript	c.1223A>T	p.His408Leu	missense_variant	8/8	5	NM_001384911.1	ENSP00000474678.1	C9J1S8
TRIM49D1	ENST00000605881.5 linkuse as main transcript	c.992A>T	p.His331Leu	missense_variant	6/6	1		ENSP00000479562.1	A0A087WVN7
TRIM49D1	ENST00000530311.6 linkuse as main transcript	c.1223A>T	p.His408Leu	missense_variant	8/8	5		ENSP00000474850.1	C9J1S8

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

100384

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00844

Gnomad SAS

AF:

0.000383

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00826

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000529

AC:

266

AN:

503282

Hom.:

Cov.:

AF XY:

0.000480

AC XY:

126

AN XY:

262586

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00868

Gnomad4 SAS exome

AF:

0.0000444

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000443

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000319

AC:

AN:

100456

Hom.:

Cov.:

AF XY:

0.000326

AC XY:

AN XY:

46002

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00846

Gnomad4 SAS

AF:

0.000385

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000104

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

Jan 09, 2024

The c.1223A>T (p.H408L) alteration is located in exon 6 (coding exon 6) of the TRIM49D1 gene. This alteration results from a A to T substitution at nucleotide position 1223, causing the histidine (H) at amino acid position 408 to be replaced by a leucine (L). 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

Uncertain

0.095

BayesDel_noAF

Benign

-0.10

CADD

Benign

0.15

DANN

Benign

0.43

DEOGEN2

Benign

0.029

T;.;T

FATHMM_MKL

Benign

0.0028

LIST_S2

Benign

0.070

.;T;.

MetaRNN

Benign

0.019

T;T;T

PrimateAI

Benign

0.42

Sift4G

Uncertain

0.030

D;D;D

Polyphen

0.0040

B;.;B

Vest4

0.089

MVP

0.69

GERP RS

-3.5

Varity_R

0.11

gMVP

0.086

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