chr6-30147765-G-C

Variant names:

• chr6-30147765-G-C
• NM_001286633.2:c.730G>C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001286633.2(TRIM40):​c.730G>C​(p.Glu244Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E244K) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: TRIM40 NM_001286633.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.678

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=0.042817473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM40	NM_001286633.2	c.730G>C	p.Glu244Gln	missense_variant	Exon 6 of 6	ENST00000396581.6	NP_001273562.1
TRIM40	NM_138700.4	c.643G>C	p.Glu215Gln	missense_variant	Exon 5 of 5		NP_619645.1
TRIM40	XM_011514306.2	c.730G>C	p.Glu244Gln	missense_variant	Exon 7 of 7		XP_011512608.1
TRIM40	XM_011514309.2	c.707G>C	p.Gly236Ala	missense_variant	Exon 5 of 5		XP_011512611.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM40	ENST00000396581.6	c.730G>C	p.Glu244Gln	missense_variant	Exon 6 of 6	1	NM_001286633.2	ENSP00000379826.1
TRIM40	ENST00000307859.4	c.643G>C	p.Glu215Gln	missense_variant	Exon 5 of 5	1		ENSP00000308310.4
TRIM40	ENST00000376724.6	c.730G>C	p.Glu244Gln	missense_variant	Exon 5 of 5	2		ENSP00000365914.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461840 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.099
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.3
DANN	Benign	0.66
DEOGEN2	Benign	0.0040	T;T;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.014	N
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.043	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.18	N;N;N
REVEL	Benign	0.037
Sift	Benign	0.14	T;T;T
Sift4G	Benign	0.38	T;T;T
Polyphen		0.0030	B;B;.
Vest4		0.048
MutPred		0.27		Gain of loop (P = 0.0312);Gain of loop (P = 0.0312);.;
MVP		0.34
MPC		0.059
ClinPred		0.098	T
GERP RS		-2.0
Varity_R		0.032
gMVP		0.047

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-30115542;