chr3-140682689-T-G

Position:

• chr3-140682689-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_152616.5(TRIM42):​c.569T>G​(p.Val190Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 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)
• Consequence: TRIM42 NM_152616.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38

Genes affected

TRIM42 (HGNC:19014): (tripartite motif containing 42) This gene encodes a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, namely a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3927273).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM42	NM_152616.5	c.569T>G	p.Val190Gly	missense_variant	2/5	ENST00000286349.4	NP_689829.3
TRIM42	XM_011512740.4	c.569T>G	p.Val190Gly	missense_variant	2/5		XP_011511042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM42	ENST00000286349.4	c.569T>G	p.Val190Gly	missense_variant	2/5	1	NM_152616.5	ENSP00000286349.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 06, 2021

The c.569T>G (p.V190G) alteration is located in exon 2 (coding exon 2) of the TRIM42 gene. This alteration results from a T to G substitution at nucleotide position 569, causing the valine (V) at amino acid position 190 to be replaced by a glycine (G). 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	0.60
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	24
DANN	Benign	0.93
DEOGEN2	Benign	0.0074	T
Eigen	Benign	-0.039
Eigen_PC	Benign	0.082
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.39	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	L
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.15
Sift	Benign	0.14	T
Sift4G	Uncertain	0.023	D
Polyphen		0.20	B
Vest4		0.40
MutPred		0.63		Loss of catalytic residue at V190 (P = 0.0752);
MVP		0.27
MPC		0.72
ClinPred		0.32	T
GERP RS		5.0
Varity_R		0.12
gMVP		0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-140401531;