6-30112427-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_007028.5(TRIM31):c.379A>G(p.Asn127Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00291 in 1,612,918 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N127K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.011 (25 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (24 hom.)
• Consequence: TRIM31 NM_007028.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.70

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0033255517).
• BP6: Variant 6-30112427-T-C is Benign according to our data. Variant chr6-30112427-T-C is described in ClinVar as [Benign]. Clinvar id is 776118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0113 (1717/152344) while in subpopulation AFR AF= 0.0345 (1434/41576). AF 95% confidence interval is 0.033. There are 25 homozygotes in gnomad4. There are 831 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 25 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM31	NM_007028.5	c.379A>G	p.Asn127Asp	missense_variant	2/9	ENST00000376734.4
TRIM31-AS1	NR_126470.1	n.395+588T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM31	ENST00000376734.4	c.379A>G	p.Asn127Asp	missense_variant	2/9	5	NM_007028.5	P1
TRIM31-AS1	ENST00000440874.1	n.395+588T>C		intron_variant, non_coding_transcript_variant		3
TRIM31	ENST00000493404.1	n.49A>G		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1718 AN: 152226 Hom.: 25 Cov.: 32

Gnomad AFR AF: 0.0346

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0109

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00131

Gnomad OTH AF: 0.0119

GnomAD3 exomes AF: 0.00333 AC: 821 AN: 246180 Hom.: 6 AF XY: 0.00270 AC XY: 362 AN XY: 134182

Gnomad AFR exome AF: 0.0357

Gnomad AMR exome AF: 0.00468

Gnomad ASJ exome AF: 0.000302

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000923

Gnomad OTH exome AF: 0.00264

GnomAD4 exome AF: 0.00203 AC: 2972 AN: 1460574 Hom.: 24 Cov.: 31 AF XY: 0.00179 AC XY: 1303 AN XY: 726600

Gnomad4 AFR exome AF: 0.0333

Gnomad4 AMR exome AF: 0.00551

Gnomad4 ASJ exome AF: 0.000268

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.00124

Gnomad4 OTH exome AF: 0.00344

GnomAD4 genome AF: 0.0113 AC: 1717 AN: 152344 Hom.: 25 Cov.: 32 AF XY: 0.0112 AC XY: 831 AN XY: 74494

Gnomad4 AFR AF: 0.0345

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00131

Gnomad4 OTH AF: 0.0118

Alfa AF: 0.00252 Hom.: 3

Bravo AF: 0.0131

TwinsUK AF: 0.00189 AC: 7

ALSPAC AF: 0.000778 AC: 3

ESP6500AA AF: 0.0334 AC: 101

ESP6500EA AF: 0.000369 AC: 2

ExAC AF: 0.00375 AC: 443

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.00125

EpiControl AF: 0.00113

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

May 21, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.72	T
BayesDel_noAF	Benign	-0.78
Cadd	Benign	2.5
Dann	Benign	0.81
DEOGEN2	Benign	0.0037	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.059	N
MetaRNN	Benign	0.0033	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.71	N
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.026
Sift	Benign	0.24	T
Sift4G	Benign	0.33	T
Polyphen		0.23	B
Vest4		0.067
MVP		0.24
MPC		0.37
ClinPred		0.012	T
GERP RS		1.1
Varity_R		0.10
gMVP		0.016

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: rs34801993; hg19: chr6-30080204;