Variant 17-75874543-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_033452.3(TRIM47):c.1857C>A(p.Asp619Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000366 in 1,367,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000037 ( 0 hom. )

Consequence

TRIM47
NM_033452.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.657

Variant links:

Genes affected

TRIM47 (HGNC:19020): (tripartite motif containing 47) Enables ubiquitin-protein transferase activity. Involved in protein ubiquitination. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

TRIM47 links:

TRIM47 (HGNC:):

TRIM47 links:

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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=0.23769125).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM47	NM_033452.3 linkuse as main transcript	c.1857C>A	p.Asp619Glu	missense_variant	6/6	ENST00000254816.6	NP_258411.2	Q96LD4-1
TRIM47	XM_005257787.5 linkuse as main transcript	c.1143C>A	p.Asp381Glu	missense_variant	6/6		XP_005257844.1	Q96LD4-2
TRIM47	XM_005257788.6 linkuse as main transcript	c.1143C>A	p.Asp381Glu	missense_variant	6/6		XP_005257845.1	Q96LD4-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM47	ENST00000254816.6 linkuse as main transcript	c.1857C>A	p.Asp619Glu	missense_variant	6/6	1	NM_033452.3	ENSP00000254816.1		Q96LD4-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000220

AC:

AN:

181462

Hom.:

AF XY:

0.0000105

AC XY:

AN XY:

95616

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000252

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

AF:

0.00000366

AC:

AN:

1367094

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

669540

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000129

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000829

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

Apr 08, 2024

The c.1857C>A (p.D619E) alteration is located in exon 6 (coding exon 6) of the TRIM47 gene. This alteration results from a C to A substitution at nucleotide position 1857, causing the aspartic acid (D) at amino acid position 619 to be replaced by a glutamic acid (E). 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

Pathogenic

0.92

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.36

CADD

Benign

0.26

DANN

Benign

0.95

DEOGEN2

Benign

0.047

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.30

LIST_S2

Benign

0.80

M_CAP

Benign

0.043

MetaRNN

Benign

0.24

MetaSVM

Benign

-0.46

MutationAssessor

Benign

1.5

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.96

REVEL

Uncertain

0.37

Sift

Uncertain

0.020

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.49

MutPred

0.47

Loss of sheet (P = 0.0457);

MVP

0.39

MPC

0.67

ClinPred

0.23

GERP RS

-10

Varity_R

0.19

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