chr1-228408476-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_016102.4(TRIM17):​c.1159G>A​(p.Gly387Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,461,870 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: not found (cov: 31)
Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

TRIM17
NM_016102.4 missense

Scores

8
8
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.35
Variant links:
Genes affected
TRIM17 (HGNC:13430): (tripartite motif containing 17) 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 protein localizes to cytoplasmic bodies. The protein is expressed almost exclusively in the testis, but its function is unknown. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.978

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM17NM_016102.4 linkc.1159G>A p.Gly387Ser missense_variant Exon 7 of 7 ENST00000366698.7 NP_057186.1 Q9Y577-1A0A024R3R3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
TRIM17ENST00000366698.7 linkc.1159G>A p.Gly387Ser missense_variant Exon 7 of 7 1 NM_016102.4 ENSP00000355659.2 Q9Y577-1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.0000157
AC:
23
AN:
1461870
Hom.:
0
Cov.:
31
AF XY:
0.0000110
AC XY:
8
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
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:
0.0000189
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.0000113

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 29, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1159G>A (p.G387S) alteration is located in exon 7 (coding exon 6) of the TRIM17 gene. This alteration results from a G to A substitution at nucleotide position 1159, causing the glycine (G) at amino acid position 387 to be replaced by a serine (S). 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
0.76
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
26
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.52
D;D;D
Eigen
Uncertain
0.63
Eigen_PC
Uncertain
0.50
FATHMM_MKL
Pathogenic
0.99
D
M_CAP
Benign
0.022
T
MetaRNN
Pathogenic
0.98
D;D;D
MetaSVM
Uncertain
0.17
D
MutationAssessor
Uncertain
2.8
M;M;M
PrimateAI
Uncertain
0.60
T
PROVEAN
Pathogenic
-5.4
D;D;D
REVEL
Uncertain
0.64
Sift
Pathogenic
0.0
D;D;D
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
1.0
D;D;D
Vest4
0.83
MutPred
0.87
Gain of disorder (P = 0.0923);Gain of disorder (P = 0.0923);Gain of disorder (P = 0.0923);
MVP
0.82
MPC
0.87
ClinPred
1.0
D
GERP RS
4.7
Varity_R
0.76
gMVP
0.63

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: rs1250128555; hg19: chr1-228596177; API