6-30147178-C-T

Variant names:

• chr6-30147178-C-T
• rs757262
• NM_001286633.2:c.635C>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.635C>T​(p.Thr212Met) 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 1,614,020 control chromosomes in the GnomAD database, including 40,801 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 (3316 hom., cov: 33)
  • Exomes 𝑓: 0.22 (37485 hom.)
• Consequence: TRIM40 NM_001286633.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• Publications: 46 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=0.0038522184).
• 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	c.635C>T	p.Thr212Met	missense_variant	Exon 4 of 6	ENST00000396581.6	NP_001273562.1
TRIM40	NM_138700.4	c.548C>T	p.Thr183Met	missense_variant	Exon 3 of 5		NP_619645.1
TRIM40	XM_011514306.2	c.635C>T	p.Thr212Met	missense_variant	Exon 5 of 7		XP_011512608.1
TRIM40	XM_011514309.2	c.635C>T	p.Thr212Met	missense_variant	Exon 4 of 5		XP_011512611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM40	ENST00000396581.6	c.635C>T	p.Thr212Met	missense_variant	Exon 4 of 6	1	NM_001286633.2	ENSP00000379826.1
TRIM40	ENST00000307859.4	c.548C>T	p.Thr183Met	missense_variant	Exon 3 of 5	1		ENSP00000308310.4
TRIM40	ENST00000376724.6	c.635C>T	p.Thr212Met	missense_variant	Exon 3 of 5	2		ENSP00000365914.2

Frequencies

GnomAD3 genomes AF: 0.198 AC: 30074 AN: 152072 Hom.: 3311 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.125

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.0905

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: 53517 AN: 251354 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: 321746 AN: 1461830 Hom.: 37485 Cov.: 55 AF XY: 0.215 AC XY: 156434 AN XY: 727220

African (AFR) AF: 0.118 AC: 3938 AN: 33478

American (AMR) AF: 0.236 AC: 10567 AN: 44724

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

East Asian (EAS) AF: 0.213 AC: 8465 AN: 39700

South Asian (SAS) AF: 0.0862 AC: 7432 AN: 86258

European-Finnish (FIN) AF: 0.287 AC: 15326 AN: 53418

Middle Eastern (MID) AF: 0.103 AC: 595 AN: 5766

European-Non Finnish (NFE) AF: 0.234 AC: 260401 AN: 1111954

Other (OTH) AF: 0.195 AC: 11798 AN: 60396

GnomAD4 genome AF: 0.198 AC: 30099 AN: 152190 Hom.: 3316 Cov.: 33 AF XY: 0.198 AC XY: 14755 AN XY: 74400

African (AFR) AF: 0.125 AC: 5205 AN: 41546

American (AMR) AF: 0.212 AC: 3239 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.125 AC: 434 AN: 3472

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

South Asian (SAS) AF: 0.0906 AC: 437 AN: 4824

European-Finnish (FIN) AF: 0.289 AC: 3059 AN: 10588

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

European-Non Finnish (NFE) AF: 0.233 AC: 15839 AN: 67978

Other (OTH) AF: 0.158 AC: 334 AN: 2114

Alfa AF: 0.212 Hom.: 15917

Bravo AF: 0.190

TwinsUK AF: 0.241 AC: 893

ALSPAC AF: 0.251 AC: 966

ESP6500AA AF: 0.126 AC: 555

ESP6500EA AF: 0.221 AC: 1899

ExAC AF: 0.210 AC: 25476

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	0.069
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	0.96
DANN	Benign	0.84
DEOGEN2	Benign	0.0011	T;T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0044	N
MetaRNN	Benign	0.0039	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.19	N;N;.
PhyloP100		-0.96
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-0.18	N;N;N
REVEL	Benign	0.081
Sift	Benign	0.57	T;T;T
Sift4G	Benign	0.48	T;T;T
Polyphen		0.018	B;B;.
Vest4		0.029
MPC		0.062
ClinPred		0.0036	T
GERP RS		-3.6
Varity_R		0.012
gMVP		0.099
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs757262; hg19: chr6-30114955; COSMIC: COSV57157758; COSMIC: COSV57157758;