6-30154382-G-T

Variant summary

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

The NM_006778.4(TRIM10):​c.1033C>A​(p.Pro345Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000242 in 1,612,896 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

TRIM10
NM_006778.4 missense

Scores

2
5
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.51
Variant links:
Genes affected
TRIM10 (HGNC:10072): (tripartite motif containing 10) 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. This protein localizes to cytoplasmic bodies. Studies in mice suggest that this protein plays a role in terminal differentiation of erythroid cells. Alternate splicing of this gene generates two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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/exons MANE UniProt
TRIM10NM_006778.4 linkuse as main transcriptc.1033C>A p.Pro345Thr missense_variant 7/7 ENST00000449742.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
TRIM10ENST00000449742.7 linkuse as main transcriptc.1033C>A p.Pro345Thr missense_variant 7/71 NM_006778.4 P1Q9UDY6-1
TRIM10ENST00000376704.3 linkuse as main transcriptc.1033C>A p.Pro345Thr missense_variant 7/81 Q9UDY6-2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
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:
0.0000325
AC:
8
AN:
246148
Hom.:
0
AF XY:
0.0000298
AC XY:
4
AN XY:
134156
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000363
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000260
AC:
38
AN:
1460710
Hom.:
0
Cov.:
35
AF XY:
0.0000220
AC XY:
16
AN XY:
726658
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152186
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74342
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000654
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:
0.0000847
Hom.:
0
Bravo
AF:
0.0000378
ExAC
AF:
0.0000340
AC:
4
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 06, 2022The c.1033C>A (p.P345T) alteration is located in exon 7 (coding exon 7) of the TRIM10 gene. This alteration results from a C to A substitution at nucleotide position 1033, causing the proline (P) at amino acid position 345 to be replaced by a threonine (T). 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
0.12
BayesDel_addAF
Benign
-0.32
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.093
T;.
Eigen
Benign
-0.013
Eigen_PC
Benign
-0.13
FATHMM_MKL
Pathogenic
0.97
D
M_CAP
Benign
0.041
D
MetaRNN
Uncertain
0.71
D;D
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.7
M;M
MutationTaster
Benign
0.75
D;D
PrimateAI
Benign
0.44
T
PROVEAN
Pathogenic
-7.0
D;D
REVEL
Benign
0.15
Sift
Uncertain
0.0040
D;D
Sift4G
Uncertain
0.0070
D;D
Polyphen
0.89
P;P
Vest4
0.46
MutPred
0.71
Gain of phosphorylation at P345 (P = 0.0337);Gain of phosphorylation at P345 (P = 0.0337);
MVP
0.30
MPC
0.29
ClinPred
0.41
T
GERP RS
3.0
Varity_R
0.032
gMVP
0.56

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: rs754026419; hg19: chr6-30122159; API