chr8-27287746-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_171982.5(TRIM35):​c.1286G>A​(p.Arg429His) variant causes a missense change. The variant allele was found at a frequency of 0.0000118 in 1,609,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

TRIM35
NM_171982.5 missense

Scores

4
12
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.46
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 Uncertain_significance. Variant got 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.791

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM35NM_171982.5 linkc.1286G>A p.Arg429His missense_variant Exon 6 of 6 ENST00000305364.9 NP_741983.2 Q9UPQ4-1
TRIM35XM_047421602.1 linkc.836G>A p.Arg279His missense_variant Exon 6 of 6 XP_047277558.1
TRIM35NM_001362813.2 linkc.*366G>A 3_prime_UTR_variant Exon 5 of 5 NP_001349742.1
TRIM35NM_001304495.2 linkc.*366G>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.1286G>A p.Arg429His missense_variant Exon 6 of 6 1 NM_171982.5 ENSP00000301924.4 Q9UPQ4-1
TRIM35ENST00000521253 linkc.*366G>A 3_prime_UTR_variant Exon 4 of 4 1 ENSP00000428770.1 E5RGB3
TRIM35ENST00000521283.1 linkc.288+290G>A intron_variant Intron 4 of 4 2 ENSP00000429356.1 H0YBF3

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000941
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000837
AC:
2
AN:
238966
Hom.:
0
AF XY:
0.00000773
AC XY:
1
AN XY:
129446
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000565
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000931
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000117
AC:
17
AN:
1457768
Hom.:
0
Cov.:
31
AF XY:
0.0000124
AC XY:
9
AN XY:
724888
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000759
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000117
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152222
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000941
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 10, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1286G>A (p.R429H) 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 1286, causing the arginine (R) at amino acid position 429 to be replaced by a histidine (H). 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
Uncertain
0.35
BayesDel_addAF
Uncertain
0.093
D
BayesDel_noAF
Benign
-0.10
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.41
T
Eigen
Uncertain
0.66
Eigen_PC
Uncertain
0.59
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.87
D
M_CAP
Uncertain
0.14
D
MetaRNN
Pathogenic
0.79
D
MetaSVM
Uncertain
0.066
D
MutationAssessor
Pathogenic
3.5
M
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-4.3
D
REVEL
Uncertain
0.55
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.0020
D
Polyphen
1.0
D
Vest4
0.74
MutPred
0.58
Gain of catalytic residue at L428 (P = 0.1289);
MVP
0.85
MPC
1.4
ClinPred
0.99
D
GERP RS
4.5
Varity_R
0.43
gMVP
0.70

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: rs1032407682; hg19: chr8-27145263; API