chr11-4385627-A-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_003141.4(TRIM21):​c.1086T>C​(p.Ser362Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00737 in 1,612,784 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0057 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0075 ( 51 hom. )

Consequence

TRIM21
NM_003141.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.01

Publications

5 publications found
Variant links:
Genes affected
TRIM21 (HGNC:11312): (tripartite motif containing 21) This gene encodes 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. The encoded protein is part of the RoSSA ribonucleoprotein, which includes a single polypeptide and one of four small RNA molecules. The RoSSA particle localizes to both the cytoplasm and the nucleus. RoSSA interacts with autoantigens in patients with Sjogren syndrome and systemic lupus erythematosus. Alternatively spliced transcript variants for this gene have been described but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.92).
BP6
Variant 11-4385627-A-G is Benign according to our data. Variant chr11-4385627-A-G is described in ClinVar as [Benign]. Clinvar id is 781807.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-2.01 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM21NM_003141.4 linkc.1086T>C p.Ser362Ser synonymous_variant Exon 7 of 7 ENST00000254436.8 NP_003132.2 P19474-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM21ENST00000254436.8 linkc.1086T>C p.Ser362Ser synonymous_variant Exon 7 of 7 1 NM_003141.4 ENSP00000254436.7 P19474-1
TRIM21ENST00000533692.1 linkc.207+51T>C intron_variant Intron 2 of 2 3 ENSP00000434053.1 H0YDP8

Frequencies

GnomAD3 genomes
AF:
0.00568
AC:
864
AN:
152202
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00425
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00228
Gnomad FIN
AF:
0.0201
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.00759
Gnomad OTH
AF:
0.00335
GnomAD2 exomes
AF:
0.00658
AC:
1622
AN:
246678
AF XY:
0.00675
show subpopulations
Gnomad AFR exome
AF:
0.00157
Gnomad AMR exome
AF:
0.00266
Gnomad ASJ exome
AF:
0.000300
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0208
Gnomad NFE exome
AF:
0.00847
Gnomad OTH exome
AF:
0.00634
GnomAD4 exome
AF:
0.00754
AC:
11017
AN:
1460464
Hom.:
51
Cov.:
32
AF XY:
0.00737
AC XY:
5354
AN XY:
726378
show subpopulations
African (AFR)
AF:
0.00117
AC:
39
AN:
33472
American (AMR)
AF:
0.00263
AC:
117
AN:
44558
Ashkenazi Jewish (ASJ)
AF:
0.000460
AC:
12
AN:
26098
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39676
South Asian (SAS)
AF:
0.00264
AC:
227
AN:
85948
European-Finnish (FIN)
AF:
0.0199
AC:
1061
AN:
53362
Middle Eastern (MID)
AF:
0.00156
AC:
9
AN:
5768
European-Non Finnish (NFE)
AF:
0.00829
AC:
9212
AN:
1111228
Other (OTH)
AF:
0.00563
AC:
340
AN:
60354
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
763
1526
2288
3051
3814
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
340
680
1020
1360
1700
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.00568
AC:
865
AN:
152320
Hom.:
6
Cov.:
32
AF XY:
0.00626
AC XY:
466
AN XY:
74480
show subpopulations
African (AFR)
AF:
0.00120
AC:
50
AN:
41578
American (AMR)
AF:
0.00425
AC:
65
AN:
15304
Ashkenazi Jewish (ASJ)
AF:
0.000288
AC:
1
AN:
3470
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5186
South Asian (SAS)
AF:
0.00249
AC:
12
AN:
4824
European-Finnish (FIN)
AF:
0.0201
AC:
213
AN:
10618
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.00759
AC:
516
AN:
68020
Other (OTH)
AF:
0.00331
AC:
7
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.504
Heterozygous variant carriers
0
39
79
118
158
197
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
20
40
60
80
100
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.00607
Hom.:
4
Bravo
AF:
0.00457
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 18, 2018
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.92
CADD
Benign
0.55
DANN
Benign
0.38
PhyloP100
-2.0
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs112534094; hg19: chr11-4406857; API