chr1-228408464-C-G

Variant summary

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

The NM_016102.4(TRIM17):​c.1171G>C​(p.Val391Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

TRIM17
NM_016102.4 missense

Scores

18

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.419
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_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.058517903).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
TRIM17NM_016102.4 linkc.1171G>C p.Val391Leu 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.1171G>C p.Val391Leu missense_variant Exon 7 of 7 1 NM_016102.4 ENSP00000355659.2 Q9Y577-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251414
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000109
AC:
16
AN:
1461870
Hom.:
0
Cov.:
30
AF XY:
0.00000963
AC XY:
7
AN XY:
727242
show subpopulations
Gnomad4 AFR exome
AF:
0.000269
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
Cov.:
32
Alfa
AF:
0.0000434
Hom.:
0
Bravo
AF:
0.0000151

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 21, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1171G>C (p.V391L) alteration is located in exon 7 (coding exon 6) of the TRIM17 gene. This alteration results from a G to C substitution at nucleotide position 1171, causing the valine (V) at amino acid position 391 to be replaced by a leucine (L). 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
0.20
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
16
DANN
Benign
0.70
DEOGEN2
Benign
0.096
T;T;T
Eigen
Benign
-0.70
Eigen_PC
Benign
-0.58
FATHMM_MKL
Benign
0.15
N
M_CAP
Benign
0.0053
T
MetaRNN
Benign
0.059
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
-0.12
N;N;N
PrimateAI
Benign
0.40
T
PROVEAN
Benign
-0.15
N;N;N
REVEL
Benign
0.039
Sift
Benign
0.90
T;T;T
Sift4G
Benign
1.0
T;T;T
Polyphen
0.12
B;B;B
Vest4
0.19
MutPred
0.45
Loss of methylation at K395 (P = 0.0741);Loss of methylation at K395 (P = 0.0741);Loss of methylation at K395 (P = 0.0741);
MVP
0.42
MPC
0.25
ClinPred
0.070
T
GERP RS
1.6
Varity_R
0.081
gMVP
0.35

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: rs368187613; hg19: chr1-228596165; API