rs757259

Variant names:

• chr6-30147765-G-A
• rs757259
• NM_001286633.2:c.730G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-30147765-G-A
• chr6-30147765-G-C
• chr6-30147765-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3315 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37467 hom.)
• Consequence: TRIM40 NM_001286633.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678
• Publications: 41 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001286633.2. 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
	TRIM40	NM_001286633.2	MANE Select	c.730G>A	p.Glu244Lys	missense	Exon 6 of 6	NP_001273562.1
	TRIM40	NM_138700.4		c.643G>A	p.Glu215Lys	missense	Exon 5 of 5	NP_619645.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM40	ENST00000396581.6	TSL:1 MANE Select	c.730G>A	p.Glu244Lys	missense	Exon 6 of 6	ENSP00000379826.1
	TRIM40	ENST00000307859.4	TSL:1	c.643G>A	p.Glu215Lys	missense	Exon 5 of 5	ENSP00000308310.4
	TRIM40	ENST00000376724.6	TSL:2	c.730G>A	p.Glu244Lys	missense	Exon 5 of 5	ENSP00000365914.2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30054 AN: 151990 Hom.: 3310 Cov.: 32

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

GnomAD2 exomes AF: 0.213 AC: 53520 AN: 251454 AF XY: 0.206

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 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.: 33 AF XY: 0.215 AC XY: 156285 AN XY: 726978

African (AFR) AF: 0.117 AC: 3933 AN: 33476

American (AMR) AF: 0.236 AC: 10566 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 3224 AN: 26136

East Asian (EAS) AF: 0.213 AC: 8463 AN: 39696

South Asian (SAS) AF: 0.0861 AC: 7424 AN: 86252

European-Finnish (FIN) AF: 0.287 AC: 15327 AN: 53418

Middle Eastern (MID) AF: 0.103 AC: 595 AN: 5768

European-Non Finnish (NFE) AF: 0.234 AC: 260118 AN: 1111458

Other (OTH) AF: 0.195 AC: 11785 AN: 60380

GnomAD4 genome AF: 0.198 AC: 30079 AN: 152108 Hom.: 3315 Cov.: 32 AF XY: 0.198 AC XY: 14747 AN XY: 74352

African (AFR) AF: 0.125 AC: 5200 AN: 41506

American (AMR) AF: 0.212 AC: 3235 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3470

East Asian (EAS) AF: 0.243 AC: 1254 AN: 5170

South Asian (SAS) AF: 0.0905 AC: 436 AN: 4820

European-Finnish (FIN) AF: 0.289 AC: 3052 AN: 10564

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.233 AC: 15839 AN: 67982

Other (OTH) AF: 0.157 AC: 332 AN: 2110

Alfa AF: 0.213 Hom.: 15950

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	3.6
DANN	Benign	0.57
DEOGEN2	Benign	0.0017	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.0096	N
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.68
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.65	N
REVEL	Benign	0.036
Sift	Benign	0.22	T
Sift4G	Benign	0.52	T
Polyphen		0.0	B
Vest4		0.055
MPC		0.065
ClinPred		0.0060	T
GERP RS		-2.0
Varity_R		0.025
gMVP		0.062
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs757259; hg19: chr6-30115542; COSMIC: COSV57157940; COSMIC: COSV57157940;