8-27287819-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_171982.5(TRIM35):​c.1213G>A​(p.Val405Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000769 in 1,611,668 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00030 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000054 ( 1 hom. )

Consequence

TRIM35
NM_171982.5 missense

Scores

1
18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.193
Variant links:
Genes affected
TRIM35 (HGNC:16285): (tripartite motif containing 35) 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. The function of this protein has not been identified. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.017506748).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM35NM_171982.5 linkc.1213G>A p.Val405Met missense_variant Exon 6 of 6 ENST00000305364.9 NP_741983.2 Q9UPQ4-1
TRIM35XM_047421602.1 linkc.763G>A p.Val255Met missense_variant Exon 6 of 6 XP_047277558.1
TRIM35NM_001362813.2 linkc.*293G>A 3_prime_UTR_variant Exon 5 of 5 NP_001349742.1
TRIM35NM_001304495.2 linkc.*293G>A 3_prime_UTR_variant Exon 4 of 4 NP_001291424.1 E5RGB3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM35ENST00000305364.9 linkc.1213G>A p.Val405Met missense_variant Exon 6 of 6 1 NM_171982.5 ENSP00000301924.4 Q9UPQ4-1
TRIM35ENST00000521253 linkc.*293G>A 3_prime_UTR_variant Exon 4 of 4 1 ENSP00000428770.1 E5RGB3
TRIM35ENST00000521283.1 linkc.288+217G>A intron_variant Intron 4 of 4 2 ENSP00000429356.1 H0YBF3

Frequencies

GnomAD3 genomes
AF:
0.000296
AC:
45
AN:
152218
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000128
AC:
31
AN:
242260
Hom.:
0
AF XY:
0.000114
AC XY:
15
AN XY:
131812
show subpopulations
Gnomad AFR exome
AF:
0.000847
Gnomad AMR exome
AF:
0.000383
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.0000485
Gnomad NFE exome
AF:
0.0000277
Gnomad OTH exome
AF:
0.000169
GnomAD4 exome
AF:
0.0000541
AC:
79
AN:
1459332
Hom.:
1
Cov.:
31
AF XY:
0.0000551
AC XY:
40
AN XY:
725912
show subpopulations
Gnomad4 AFR exome
AF:
0.000687
Gnomad4 AMR exome
AF:
0.000405
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000931
Gnomad4 FIN exome
AF:
0.0000380
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.0000830
GnomAD4 genome
AF:
0.000295
AC:
45
AN:
152336
Hom.:
0
Cov.:
32
AF XY:
0.000282
AC XY:
21
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.000962
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000653
Hom.:
0
Bravo
AF:
0.000298
ESP6500AA
AF:
0.000682
AC:
3
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000157
AC:
19

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jun 24, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1213G>A (p.V405M) alteration is located in exon 6 (coding exon 6) of the TRIM35 gene. This alteration results from a G to A substitution at nucleotide position 1213, causing the valine (V) at amino acid position 405 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
18
DANN
Uncertain
0.98
DEOGEN2
Benign
0.014
T
Eigen
Benign
-0.71
Eigen_PC
Benign
-0.71
FATHMM_MKL
Benign
0.12
N
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.047
D
MetaRNN
Benign
0.018
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.1
L
PrimateAI
Benign
0.48
T
PROVEAN
Benign
0.19
N
REVEL
Benign
0.023
Sift
Benign
0.23
T
Sift4G
Benign
0.26
T
Polyphen
0.44
B
Vest4
0.048
MVP
0.47
MPC
0.51
ClinPred
0.0054
T
GERP RS
0.052
Varity_R
0.044
gMVP
0.15

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

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

Other links and lift over

dbSNP: rs148875535; hg19: chr8-27145336; COSMIC: COSV59522608; API