chr6-30147178-C-T

Position:

• chr6-30147178-C-T

Variant summary

Our verdict is Benign. Variant got -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. 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.

• 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

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
TRIM40	NM_001286633.2	c.635C>T	p.Thr212Met	missense_variant	4/6	ENST00000396581.6	NP_001273562.1
TRIM40	NM_138700.4	c.548C>T	p.Thr183Met	missense_variant	3/5		NP_619645.1
TRIM40	XM_011514306.2	c.635C>T	p.Thr212Met	missense_variant	5/7		XP_011512608.1
TRIM40	XM_011514309.2	c.635C>T	p.Thr212Met	missense_variant	4/5		XP_011512611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM40	ENST00000396581.6	c.635C>T	p.Thr212Met	missense_variant	4/6	1	NM_001286633.2	ENSP00000379826	P1
TRIM40	ENST00000307859.4	c.548C>T	p.Thr183Met	missense_variant	3/5	1		ENSP00000308310
TRIM40	ENST00000376724.6	c.635C>T	p.Thr212Met	missense_variant	3/5	2		ENSP00000365914	P1

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

GnomAD3 exomes AF: 0.213 AC: 53517 AN: 251354 Hom.: 6453 AF XY: 0.206 AC XY: 27973 AN XY: 135848

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: 0.0827

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

Gnomad4 AFR exome AF: 0.118

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.123

Gnomad4 EAS exome AF: 0.213

Gnomad4 SAS exome AF: 0.0862

Gnomad4 FIN exome AF: 0.287

Gnomad4 NFE exome AF: 0.234

Gnomad4 OTH exome AF: 0.195

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

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.212

Gnomad4 ASJ AF: 0.125

Gnomad4 EAS AF: 0.243

Gnomad4 SAS AF: 0.0906

Gnomad4 FIN AF: 0.289

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.158

Alfa AF: 0.212 Hom.: 7906

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;.
MutationTaster	Benign	1.0	P;P;P
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

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

Publications

LitVar

Other links and lift over

dbSNP: rs757262; hg19: chr6-30114955; COSMIC: COSV57157758; COSMIC: COSV57157758;