6-30147178-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001286633.2(TRIM40):​c.635C>G​(p.Thr212Arg) 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. 16/24 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: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>G	p.Thr212Arg	missense	Exon 4 of 6	NP_001273562.1
	TRIM40	NM_138700.4		c.548C>G	p.Thr183Arg	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>G	p.Thr212Arg	missense	Exon 4 of 6	ENSP00000379826.1
	TRIM40	ENST00000307859.4	TSL:1	c.548C>G	p.Thr183Arg	missense	Exon 3 of 5	ENSP00000308310.4
	TRIM40	ENST00000376724.6	TSL:2	c.635C>G	p.Thr212Arg	missense	Exon 3 of 5	ENSP00000365914.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	7.4
DANN	Benign	0.88
DEOGEN2	Benign	0.00029	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.022	N
M_CAP	Benign	0.044	D
MetaRNN	Benign	0.088	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.88	L
PhyloP100		-0.96
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.71	N
REVEL	Benign	0.14
Sift	Benign	0.041	D
Sift4G	Uncertain	0.048	D
Polyphen		0.83	P
Vest4		0.24
MutPred		0.49		Gain of MoRF binding (P = 0.0322)
MVP		0.48
MPC		0.24
ClinPred		0.30	T
GERP RS		-3.6
Varity_R		0.043
gMVP		0.13
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.21		Position offset: 31

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs757262; hg19: chr6-30114955;