6-30103766-G-C

Variant summary

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

The NM_007028.5(TRIM31):c.1048C>G(p.Pro350Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,758 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TRIM31 NM_007028.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.275

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]

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=0.06728995).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM31	NM_007028.5	c.1048C>G	p.Pro350Ala	missense_variant	9/9	ENST00000376734.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM31	ENST00000376734.4	c.1048C>G	p.Pro350Ala	missense_variant	9/9	5	NM_007028.5	P1
TRIM31	ENST00000471695.1	n.580C>G		non_coding_transcript_exon_variant	3/4	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460758 Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2 AN XY: 726690

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: 0.00000270

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2023

The c.1048C>G (p.P350A) alteration is located in exon 9 (coding exon 8) of the TRIM31 gene. This alteration results from a C to G substitution at nucleotide position 1048, causing the proline (P) at amino acid position 350 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	15
Dann	Uncertain	0.99
DEOGEN2	Benign	0.0059	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.078	N
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.067	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.22	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.064
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.11	B
Vest4		0.14
MutPred		0.18		Loss of catalytic residue at P349 (P = 0.016);
MVP		0.41
MPC		0.24
ClinPred		0.17	T
GERP RS		0.49
Varity_R		0.049
gMVP		0.0099

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: chr6-30071543;