dbSNP rs757259: TRIM40:p.Glu244Lys (chr6-30147765-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001286633.2(TRIM40):c.730G>A(p.Glu244Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,613,416 control chromosomes in the GnomAD database, including 40,782 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 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 0.20 ( 3315 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37467 hom. )

Consequence

TRIM40
NM_001286633.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.678

Variant links:

Genes affected

TRIM40 (HGNC:18736): (tripartite motif containing 40) This gene encodes a member of the tripartite motif (TRIM) protein family. The encoded protein may play a role as a negative regulator against inflammation and carcinogenesis in the gastrointestinal tract. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Feb 2014]

TRIM40 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004510671).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.231 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM40	NM_001286633.2 link	c.730G>A	p.Glu244Lys	missense_variant	Exon 6 of 6	ENST00000396581.6	NP_001273562.1	Q6P9F5-1A0A1U9X8U1
TRIM40	NM_138700.4 link	c.643G>A	p.Glu215Lys	missense_variant	Exon 5 of 5		NP_619645.1	Q6P9F5-2
TRIM40	XM_011514306.2 link	c.730G>A	p.Glu244Lys	missense_variant	Exon 7 of 7		XP_011512608.1	Q6P9F5-1A0A1U9X8U1
TRIM40	XM_011514309.2 link	c.707G>A	p.Gly236Glu	missense_variant	Exon 5 of 5		XP_011512611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TRIM40	ENST00000396581.6 link	c.730G>A	p.Glu244Lys	missense_variant	Exon 6 of 6	1	NM_001286633.2	ENSP00000379826.1	Q6P9F5-1
TRIM40	ENST00000307859.4 link	c.643G>A	p.Glu215Lys	missense_variant	Exon 5 of 5	1		ENSP00000308310.4	Q6P9F5-2
TRIM40	ENST00000376724.6 link	c.730G>A	p.Glu244Lys	missense_variant	Exon 5 of 5	2		ENSP00000365914.2	Q6P9F5-1

Frequencies

GnomAD3 genomes

AF:

0.198

AC:

30054

AN:

151990

Hom.:

3310

Cov.:

show subpopulations

Gnomad AFR

AF:

0.125

Gnomad AMI

AF:

0.304

Gnomad AMR

AF:

0.211

Gnomad ASJ

AF:

0.124

Gnomad EAS

AF:

0.242

Gnomad SAS

AF:

0.0904

Gnomad FIN

AF:

0.289

Gnomad MID

AF:

0.0791

Gnomad NFE

AF:

0.233

Gnomad OTH

AF:

0.159

GnomAD3 exomes

AF:

0.213

AC:

53520

AN:

251454

Hom.:

6453

AF XY:

0.206

AC XY:

27983

AN XY:

135908

show subpopulations

Gnomad AFR exome

AF:

0.124

Gnomad AMR exome

AF:

0.233

Gnomad ASJ exome

AF:

0.130

Gnomad EAS exome

AF:

0.268

Gnomad SAS exome

AF:

0.0825

Gnomad FIN exome

AF:

0.295

Gnomad NFE exome

AF:

0.238

Gnomad OTH exome

AF:

0.194

GnomAD4 exome

AF:

0.220

AC:

321435

AN:

1461308

Hom.:

37467

Cov.:

AF XY:

0.215

AC XY:

156285

AN XY:

726978

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.236

Gnomad4 ASJ exome

AF:

0.123

Gnomad4 EAS exome

AF:

0.213

Gnomad4 SAS exome

AF:

0.0861

Gnomad4 FIN exome

AF:

0.287

Gnomad4 NFE exome

AF:

0.234

Gnomad4 OTH exome

AF:

0.195

GnomAD4 genome

AF:

0.198

AC:

30079

AN:

152108

Hom.:

3315

Cov.:

AF XY:

0.198

AC XY:

14747

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.125

Gnomad4 AMR

AF:

0.212

Gnomad4 ASJ

AF:

0.124

Gnomad4 EAS

AF:

0.243

Gnomad4 SAS

AF:

0.0905

Gnomad4 FIN

AF:

0.289

Gnomad4 NFE

AF:

0.233

Gnomad4 OTH

AF:

0.157

Alfa

AF:

0.215

Hom.:

7686

Bravo

AF:

0.190

TwinsUK

AF:

0.241

AC:

894

ALSPAC

AF:

0.250

AC:

962

ESP6500AA

AF:

0.126

AC:

555

ESP6500EA

AF:

0.221

AC:

1899

ExAC

AF:

0.210

AC:

25474

Asia WGS

AF:

0.130

AC:

453

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.62

CADD

Benign

3.6

DANN

Benign

0.57

DEOGEN2

Benign

0.0017

T;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0096

MetaRNN

Benign

0.0045

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.

PrimateAI

Benign

0.39

PROVEAN

Benign

0.65

N;N;N

REVEL

Benign

0.036

Sift

Benign

0.22

T;T;T

Sift4G

Benign

0.52

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.055

MPC

0.065

ClinPred

0.0060

GERP RS

-2.0

Varity_R

0.025

gMVP

0.062

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over