6-30110633-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP6

The NM_007028.5(TRIM31):c.559C>T(p.Leu187Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000292 in 1,614,214 control chromosomes in the GnomAD database, including 42 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.00033 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00029 (37 hom.)
• Consequence: TRIM31 NM_007028.5 missense
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: 0.249

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

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.022225678).
• BP6: Variant 6-30110633-G-A is Benign according to our data. Variant chr6-30110633-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 782821.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM31	NM_007028.5	c.559C>T	p.Leu187Phe	missense_variant	4/9	ENST00000376734.4
TRIM31-AS1	NR_126470.1	n.274-1085G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM31	ENST00000376734.4	c.559C>T	p.Leu187Phe	missense_variant	4/9	5	NM_007028.5	P1
TRIM31-AS1	ENST00000440874.1	n.274-1085G>A		intron_variant, non_coding_transcript_variant		3
TRIM31	ENST00000480808.1	n.105C>T		non_coding_transcript_exon_variant	2/3	3
TRIM31	ENST00000485864.5	n.249C>T		non_coding_transcript_exon_variant	3/6	3

Frequencies

GnomAD3 genomes AF: 0.000237 AC: 36 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000235 AC: 59 AN: 251486 Hom.: 1 AF XY: 0.000191 AC XY: 26 AN XY: 135914

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00201

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000879

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.000289 AC: 422 AN: 1461890 Hom.: 37 Cov.: 33 AF XY: 0.000249 AC XY: 181 AN XY: 727244

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000268

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00184

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000108

Gnomad4 OTH exome AF: 0.00533

GnomAD4 genome AF: 0.000328 AC: 50 AN: 152324 Hom.: 5 Cov.: 32 AF XY: 0.000134 AC XY: 10 AN XY: 74482

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000849

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00327

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.000521 Hom.: 0

Bravo AF: 0.000389

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

ExAC AF: 0.000214 AC: 26

Asia WGS AF: 0.0330 AC: 113 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 11, 2023

The c.559C>T (p.L187F) alteration is located in exon 4 (coding exon 3) of the TRIM31 gene. This alteration results from a C to T substitution at nucleotide position 559, causing the leucine (L) at amino acid position 187 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jun 22, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.61	T
BayesDel_noAF	Benign	-0.65
Cadd	Benign	8.1
Dann	Benign	0.88
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.042	N
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.022	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.36	N
REVEL	Benign	0.054
Sift	Benign	0.26	T
Sift4G	Benign	0.096	T
Polyphen		0.63	P
Vest4		0.074
MVP		0.30
MPC		0.26
ClinPred		0.016	T
GERP RS		-0.87
Varity_R		0.029
gMVP		0.026

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

LitVar

Other links and lift over

dbSNP: rs372346318; hg19: chr6-30078410;