6-30147765-G-T

Variant names:

• chr6-30147765-G-T
• rs757259
• NM_001286633.2:c.730G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001286633.2(TRIM40):​c.730G>T​(p.Glu244*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRIM40 NM_001286633.2 stop_gained
• 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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM40	NM_001286633.2	c.730G>T	p.Glu244*	stop_gained	Exon 6 of 6	ENST00000396581.6	NP_001273562.1
TRIM40	NM_138700.4	c.643G>T	p.Glu215*	stop_gained	Exon 5 of 5		NP_619645.1
TRIM40	XM_011514306.2	c.730G>T	p.Glu244*	stop_gained	Exon 7 of 7		XP_011512608.1
TRIM40	XM_011514309.2	c.707G>T	p.Gly236Val	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>T	p.Glu244*	stop_gained	Exon 6 of 6	1	NM_001286633.2	ENSP00000379826.1
TRIM40	ENST00000307859.4	c.643G>T	p.Glu215*	stop_gained	Exon 5 of 5	1		ENSP00000308310.4
TRIM40	ENST00000376724.6	c.730G>T	p.Glu244*	stop_gained	Exon 5 of 5	2		ENSP00000365914.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 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: 8.99e-7

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
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	34
DANN	Benign	0.94
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.013	N
Vest4		0.074
GERP RS		-2.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.32		Position offset: -40

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

Publications

LitVar

Other links and lift over

dbSNP: rs757259; hg19: chr6-30115542;