6-30147178-C-A

Position:

• chr6-30147178-C-A

Variant summary

Our verdict is Likely benign. Variant got -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. 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: not found (cov: 33)
• 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 Likely_benign. Variant got -2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM40	NM_001286633.2	c.635C>A	p.Thr212Lys	missense_variant	4/6	ENST00000396581.6	NP_001273562.1
TRIM40	NM_138700.4	c.548C>A	p.Thr183Lys	missense_variant	3/5		NP_619645.1
TRIM40	XM_011514306.2	c.635C>A	p.Thr212Lys	missense_variant	5/7		XP_011512608.1
TRIM40	XM_011514309.2	c.635C>A	p.Thr212Lys	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>A	p.Thr212Lys	missense_variant	4/6	1	NM_001286633.2	ENSP00000379826	P1
TRIM40	ENST00000307859.4	c.548C>A	p.Thr183Lys	missense_variant	3/5	1		ENSP00000308310
TRIM40	ENST00000376724.6	c.635C>A	p.Thr212Lys	missense_variant	3/5	2		ENSP00000365914	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 55

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;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;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.31	T
PROVEAN	Benign	0.55	N;N;N
REVEL	Benign	0.083
Sift	Benign	0.41	T;T;T
Sift4G	Benign	0.080	T;T;T
Polyphen		0.59	P;P;.
Vest4		0.22
MutPred		0.51		Gain of ubiquitination at T212 (P = 0.0198);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

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

Publications

LitVar

Other links and lift over

dbSNP: rs757262; hg19: chr6-30114955;