11-5610891-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000380097.8(TRIM6):ā€‹c.1100A>Gā€‹(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 (ā˜…).

Frequency

Genomes: š‘“ 0.0035 ( 3 hom., cov: 32)
Exomes š‘“: 0.0049 ( 46 hom. )

Consequence

TRIM6
ENST00000380097.8 missense

Scores

18

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.46
Variant links:
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]

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ACMG classification

Classification made for transcript

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
TRIM6NM_001003818.3 linkuse as main transcriptc.1100A>G p.His367Arg missense_variant 8/8 ENST00000380097.8 NP_001003818.1
TRIM6-TRIM34NM_001003819.4 linkuse as main transcriptc.985+330A>G intron_variant NP_001003819.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
TRIM6ENST00000380097.8 linkuse as main transcriptc.1100A>G p.His367Arg missense_variant 8/81 NM_001003818.3 ENSP00000369440 Q9C030-2

Frequencies

GnomAD3 genomes
AF:
0.00350
AC:
533
AN:
152204
Hom.:
3
Cov.:
32
show subpopulations
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
show subpopulations
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
show subpopulations
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
show subpopulations
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
LINK: link

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenMar 01, 2023TRIM6: 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;.;.;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;N;N;N;N;N;N;N;D
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150778640; hg19: chr11-5632121; COSMIC: COSV105843429; COSMIC: COSV105843429; API