chr3-140678548-C-T

Variant names:

• chr3-140678548-C-T
• rs770273666
• NM_152616.5:c.319C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_152616.5(TRIM42):​c.319C>T​(p.Arg107Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,613,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R107S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00015 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000049 (0 hom.)
• Consequence: TRIM42 NM_152616.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.756
• Publications: 1 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07075566).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152616.5. 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
	TRIM42	NM_152616.5	MANE Select	c.319C>T	p.Arg107Cys	missense	Exon 1 of 5	NP_689829.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM42	ENST00000286349.4	TSL:1 MANE Select	c.319C>T	p.Arg107Cys	missense	Exon 1 of 5	ENSP00000286349.3	Q8IWZ5-1

Frequencies

GnomAD3 genomes AF: 0.000151 AC: 23 AN: 152070 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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: 0.0000486 AC: 12 AN: 247124 AF XY: 0.0000596

Gnomad AFR exome AF: 0.000257

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: 0.0000543

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000486 AC: 71 AN: 1461466 Hom.: 0 Cov.: 31 AF XY: 0.0000550 AC XY: 40 AN XY: 727004

African (AFR) AF: 0.000329 AC: 11 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53320

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000513 AC: 57 AN: 1111782

Other (OTH) AF: 0.00 AC: 0 AN: 60370

GnomAD4 genome AF: 0.000151 AC: 23 AN: 152070 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74282

African (AFR) AF: 0.000531 AC: 22 AN: 41394

American (AMR) AF: 0.0000655 AC: 1 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68004

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000117 Hom.: 0

Bravo AF: 0.000113

ExAC AF: 0.0000660 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.22
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.76
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.12
Sift	Uncertain	0.028	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.071	B
Vest4		0.32
MVP		0.33
MPC		0.32
ClinPred		0.075	T
GERP RS		2.8
PromoterAI		0.0012	Neutral
Varity_R		0.083
gMVP		0.45
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs770273666; hg19: chr3-140397390; COSMIC: COSV53888059;