chr11-5610891-A-G

Position:

• chr11-5610891-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001003818.3(TRIM6):​c.1100A>G​(p.His367Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00481 in 1,614,212 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0035 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0049 (46 hom.)
• Consequence: TRIM6 NM_001003818.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.46

Genes affected

TRIM6 (HGNC:16277): (tripartite motif containing 6) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, B-box type 1 and B-box type 2 domain, and a coiled-coil region. The protein localizes to the nucleus, but its specific function has not been identified. This gene is mapped to chromosome 11p15, where it resides within a TRIM gene cluster. Alternative splicing results in multiple transcript variants. A read-through transcript from this gene into the downstream TRIM34 gene has also been observed, which results in a fusion product from these neighboring family members. [provided by RefSeq, Oct 2010]

TRIM6-TRIM34 (HGNC:33440): (TRIM6-TRIM34 readthrough) The protein encoded by this gene is a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. This gene represents a readthrough transcript from genes TRIM6 and TRIM34, and it was described as a splice variant of TRIM34. This gene is mapped to chromosome 11p15, where it resides within a TRIM gene cluster. [provided by RefSeq, Nov 2009]

ENSG00000239920 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035454333).
• BP6: Variant 11-5610891-A-G is Benign according to our data. Variant chr11-5610891-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2641541.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM6	NM_001003818.3	c.1100A>G	p.His367Arg	missense_variant	8/8	ENST00000380097.8	NP_001003818.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM6	ENST00000380097.8	c.1100A>G	p.His367Arg	missense_variant	8/8	1	NM_001003818.3	ENSP00000369440.3
TRIM6-TRIM34	ENST00000354852.5	c.985+330A>G		intron_variant		2		ENSP00000346916.5
ENSG00000239920	ENST00000380259.7	n.*422-15541T>C		intron_variant		5		ENSP00000369609.3

Frequencies

GnomAD3 genomes AF: 0.00350 AC: 533 AN: 152204 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000893

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00366

Gnomad ASJ AF: 0.00519

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00766

Gnomad FIN AF: 0.00245

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00511

Gnomad OTH AF: 0.00430

GnomAD3 exomes AF: 0.00409 AC: 1028 AN: 251492 Hom.: 9 AF XY: 0.00457 AC XY: 621 AN XY: 135920

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.00156

Gnomad ASJ exome AF: 0.00387

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0102

Gnomad FIN exome AF: 0.00212

Gnomad NFE exome AF: 0.00489

Gnomad OTH exome AF: 0.00179

GnomAD4 exome AF: 0.00495 AC: 7235 AN: 1461890 Hom.: 46 Cov.: 34 AF XY: 0.00520 AC XY: 3785 AN XY: 727248

Gnomad4 AFR exome AF: 0.000777

Gnomad4 AMR exome AF: 0.00154

Gnomad4 ASJ exome AF: 0.00417

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0105

Gnomad4 FIN exome AF: 0.00217

Gnomad4 NFE exome AF: 0.00515

Gnomad4 OTH exome AF: 0.00407

GnomAD4 genome AF: 0.00349 AC: 532 AN: 152322 Hom.: 3 Cov.: 32 AF XY: 0.00326 AC XY: 243 AN XY: 74486

Gnomad4 AFR AF: 0.000890

Gnomad4 AMR AF: 0.00366

Gnomad4 ASJ AF: 0.00519

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00746

Gnomad4 FIN AF: 0.00245

Gnomad4 NFE AF: 0.00512

Gnomad4 OTH AF: 0.00426

Alfa AF: 0.00492 Hom.: 3

Bravo AF: 0.00313

TwinsUK AF: 0.00512 AC: 19

ALSPAC AF: 0.00415 AC: 16

ESP6500AA AF: 0.000909 AC: 4

ESP6500EA AF: 0.00582 AC: 50

ExAC AF: 0.00412 AC: 500

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.00458

EpiControl AF: 0.00450

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

TRIM6: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.22
CADD	Benign	15
DANN	Benign	0.93
DEOGEN2	Benign	0.038	T;.;.;.;.;.;.;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.19
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.57	T;.;.;T;.;.;T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.0035	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.99	L;.;.;.;.;.;.;.
PROVEAN	Benign	-2.2	N;N;N;N;N;N;N;.
REVEL	Benign	0.27
Sift	Benign	0.26	T;T;T;T;T;T;T;.
Sift4G	Benign	0.36	T;T;T;T;T;T;T;T
Polyphen		0.18	B;.;B;B;.;.;.;B
Vest4		0.32
MVP		0.49
MPC		0.030
ClinPred		0.0073	T
GERP RS		4.2
Varity_R		0.077
gMVP		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.10		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: rs150778640; hg19: chr11-5632121; COSMIC: COSV105843429; COSMIC: COSV105843429;