rs757262

Variant names:

• chr6-30147178-C-A
• rs757262
• NM_001286633.2:c.635C>A

Your query was ambiguous. Multiple possible variants found:

• chr6-30147178-C-A
• chr6-30147178-C-G
• chr6-30147178-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001286633.2(TRIM40):​c.635C>A​(p.Thr212Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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: not found (cov: 33)
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058386087).

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.635C>A	p.Thr212Lys	missense	Exon 4 of 6	NP_001273562.1
	TRIM40	NM_138700.4		c.548C>A	p.Thr183Lys	missense	Exon 3 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.635C>A	p.Thr212Lys	missense	Exon 4 of 6	ENSP00000379826.1
	TRIM40	ENST00000307859.4	TSL:1	c.548C>A	p.Thr183Lys	missense	Exon 3 of 5	ENSP00000308310.4
	TRIM40	ENST00000376724.6	TSL:2	c.635C>A	p.Thr212Lys	missense	Exon 3 of 5	ENSP00000365914.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 15917

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	7.1
DANN	Benign	0.83
DEOGEN2	Benign	0.000097	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.021	N
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		-0.96
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.55	N
REVEL	Benign	0.083
Sift	Benign	0.41	T
Sift4G	Benign	0.080	T
Polyphen		0.59	P
Vest4		0.22
MutPred		0.51		Gain of ubiquitination at T212 (P = 0.0198)
MVP		0.38
MPC		0.21
ClinPred		0.22	T
GERP RS		-3.6
Varity_R		0.027
gMVP		0.12
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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;