NM_152616.5:c.1736C>A

Variant names:

• chr3-140688418-C-A
• rs9876490
• NM_152616.5:c.1736C>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152616.5(TRIM42):​c.1736C>A​(p.Ala579Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 1,613,836 control chromosomes in the GnomAD database, including 243,886 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

• Frequency:
  • Genomes: 𝑓 0.48 (18651 hom., cov: 32)
  • Exomes 𝑓: 0.55 (225235 hom.)
• Consequence: TRIM42 NM_152616.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.217

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=3.812517E-5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.565 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM42	NM_152616.5	c.1736C>A	p.Ala579Glu	missense_variant	Exon 3 of 5	ENST00000286349.4	NP_689829.3
TRIM42	XM_011512740.4	c.1736C>A	p.Ala579Glu	missense_variant	Exon 3 of 5		XP_011511042.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM42	ENST00000286349.4	c.1736C>A	p.Ala579Glu	missense_variant	Exon 3 of 5	1	NM_152616.5	ENSP00000286349.3

Frequencies

GnomAD3 genomes AF: 0.482 AC: 73251 AN: 151872 Hom.: 18634 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.478

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.559

Gnomad EAS AF: 0.385

Gnomad SAS AF: 0.437

Gnomad FIN AF: 0.565

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.569

Gnomad OTH AF: 0.521

GnomAD3 exomes AF: 0.519 AC: 130180 AN: 251052 Hom.: 34497 AF XY: 0.521 AC XY: 70752 AN XY: 135720

Gnomad AFR exome AF: 0.302

Gnomad AMR exome AF: 0.521

Gnomad ASJ exome AF: 0.561

Gnomad EAS exome AF: 0.393

Gnomad SAS exome AF: 0.443

Gnomad FIN exome AF: 0.565

Gnomad NFE exome AF: 0.576

Gnomad OTH exome AF: 0.539

GnomAD4 exome AF: 0.552 AC: 806223 AN: 1461846 Hom.: 225235 Cov.: 70 AF XY: 0.549 AC XY: 399119 AN XY: 727228

Gnomad4 AFR exome AF: 0.304

Gnomad4 AMR exome AF: 0.525

Gnomad4 ASJ exome AF: 0.555

Gnomad4 EAS exome AF: 0.381

Gnomad4 SAS exome AF: 0.448

Gnomad4 FIN exome AF: 0.560

Gnomad4 NFE exome AF: 0.574

Gnomad4 OTH exome AF: 0.538

GnomAD4 genome AF: 0.482 AC: 73297 AN: 151990 Hom.: 18651 Cov.: 32 AF XY: 0.482 AC XY: 35823 AN XY: 74270

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.559

Gnomad4 EAS AF: 0.385

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.565

Gnomad4 NFE AF: 0.569

Gnomad4 OTH AF: 0.526

Alfa AF: 0.555 Hom.: 60467

Bravo AF: 0.474

TwinsUK AF: 0.582 AC: 2158

ALSPAC AF: 0.573 AC: 2208

ESP6500AA AF: 0.314 AC: 1382

ESP6500EA AF: 0.579 AC: 4982

ExAC AF: 0.513 AC: 62311

Asia WGS AF: 0.439 AC: 1527 AN: 3478

EpiCase AF: 0.580

EpiControl AF: 0.569

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.66	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.83
DANN	Benign	0.75
DEOGEN2	Benign	0.00039	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.051	N
LIST_S2	Benign	0.66	T
MetaRNN	Benign	0.000038	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.030	N
REVEL	Benign	0.022
Sift	Benign	0.053	T
Sift4G	Benign	0.10	T
Polyphen		0.010	B
Vest4		0.055
MPC		0.27
ClinPred		0.0072	T
GERP RS		-1.2
Varity_R		0.060
gMVP		0.29

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

Publications

LitVar

Other links and lift over

dbSNP: rs9876490; hg19: chr3-140407260; COSMIC: COSV53881008;