8-27287861-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_171982.5(TRIM35):​c.1171G>T​(p.Asp391Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

TRIM35
NM_171982.5 missense

Scores

1
12
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.19
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM35NM_171982.5 linkc.1171G>T p.Asp391Tyr missense_variant Exon 6 of 6 ENST00000305364.9 NP_741983.2 Q9UPQ4-1
TRIM35XM_047421602.1 linkc.721G>T p.Asp241Tyr missense_variant Exon 6 of 6 XP_047277558.1
TRIM35NM_001362813.2 linkc.*251G>T 3_prime_UTR_variant Exon 5 of 5 NP_001349742.1
TRIM35NM_001304495.2 linkc.*251G>T 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.1171G>T p.Asp391Tyr missense_variant Exon 6 of 6 1 NM_171982.5 ENSP00000301924.4 Q9UPQ4-1
TRIM35ENST00000521253 linkc.*251G>T 3_prime_UTR_variant Exon 4 of 4 1 ENSP00000428770.1 E5RGB3
TRIM35ENST00000521283.1 linkc.288+175G>T intron_variant Intron 4 of 4 2 ENSP00000429356.1 H0YBF3

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
May 08, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1171G>T (p.D391Y) alteration is located in exon 6 (coding exon 6) of the TRIM35 gene. This alteration results from a G to T substitution at nucleotide position 1171, causing the aspartic acid (D) at amino acid position 391 to be replaced by a tyrosine (Y). 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
Pathogenic
0.86
BayesDel_addAF
Uncertain
0.13
D
BayesDel_noAF
Uncertain
-0.060
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.017
T
Eigen
Uncertain
0.26
Eigen_PC
Benign
0.22
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Benign
0.83
T
M_CAP
Uncertain
0.22
D
MetaRNN
Uncertain
0.73
D
MetaSVM
Benign
-0.68
T
MutationAssessor
Uncertain
2.5
M
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.9
N
REVEL
Uncertain
0.38
Sift
Uncertain
0.012
D
Sift4G
Uncertain
0.0060
D
Polyphen
0.90
P
Vest4
0.60
MutPred
0.56
Loss of disorder (P = 0.0466);
MVP
0.78
MPC
1.4
ClinPred
0.97
D
GERP RS
3.6
Varity_R
0.29
gMVP
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-27145378; API