NM_007028.5:c.1022C>T

Variant names:

• chr6-30104104-G-A
• rs1768460953
• NM_007028.5:c.1022C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007028.5(TRIM31):​c.1022C>T​(p.Ala341Val) variant causes a missense, splice region 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. 19/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM31 NM_007028.5 missense, splice_region
• Scores: Splicing: ADA: 0.02214
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55
• Publications: 0 publications found

Genes affected

TRIM31 (HGNC:16289): (tripartite motif containing 31) This gene encodes a protein that functions as an E3 ubiquitin-protein ligase. This gene shows altered expression in certain tumors and may be a negative regulator of cell growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2016]

TRIM31-AS1 (HGNC:39761): (TRIM31 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.073682696).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007028.5. 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
	TRIM31	NM_007028.5	MANE Select	c.1022C>T	p.Ala341Val	missense splice_region	Exon 8 of 9	NP_008959.3
	TRIM31	NR_134870.2		n.1132C>T		splice_region non_coding_transcript_exon	Exon 8 of 10
	TRIM31	NR_134871.2		n.1065C>T		splice_region non_coding_transcript_exon	Exon 7 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM31	ENST00000376734.4	TSL:5 MANE Select	c.1022C>T	p.Ala341Val	missense splice_region	Exon 8 of 9	ENSP00000365924.3	Q9BZY9-1
	TRIM31	ENST00000873800.1		c.1022C>T	p.Ala341Val	missense splice_region	Exon 7 of 8	ENSP00000543859.1
	TRIM31	ENST00000960267.1		c.1022C>T	p.Ala341Val	missense splice_region	Exon 8 of 9	ENSP00000630326.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000468 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	17
DANN	Benign	0.95
DEOGEN2	Benign	0.0040	T
Eigen	Benign	-0.79
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.20	N
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.074	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		1.6
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.12
Sift	Benign	0.030	D
Sift4G	Uncertain	0.041	D
Polyphen		0.0010	B
Vest4		0.13
MutPred		0.19		Gain of glycosylation at S339 (P = 0.1063)
MVP		0.51
MPC		0.23
ClinPred		0.10	T
GERP RS		2.5
Varity_R		0.026
gMVP		0.012
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.022
dbscSNV1_RF	Benign	0.22
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

Other links and lift over

dbSNP: rs1768460953; hg19: chr6-30071881;