NM_016102.4:c.1239G>C

Variant names:

• chr1-228408396-C-G
• rs1194942172
• NM_016102.4:c.1239G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016102.4(TRIM17):​c.1239G>C​(p.Glu413Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 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: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM17 NM_016102.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0170
• Publications: 0 publications found

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]

ENSG00000231563 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24990141).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016102.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM17	NM_016102.4	MANE Select	c.1239G>C	p.Glu413Asp	missense	Exon 7 of 7	NP_057186.1	Q9Y577-1
	TRIM17	NM_001024940.3		c.1239G>C	p.Glu413Asp	missense	Exon 7 of 7	NP_001020111.1	Q9Y577-1
	TRIM17	NM_001438323.1		c.1158G>C	p.Glu386Asp	missense	Exon 7 of 7	NP_001425252.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM17	ENST00000366698.7	TSL:1 MANE Select	c.1239G>C	p.Glu413Asp	missense	Exon 7 of 7	ENSP00000355659.2	Q9Y577-1
	TRIM17	ENST00000295033.7	TSL:1	c.1239G>C	p.Glu413Asp	missense	Exon 7 of 7	ENSP00000295033.3	Q9Y577-1
	TRIM17	ENST00000366697.6	TSL:2	c.1239G>C	p.Glu413Asp	missense	Exon 6 of 6	ENSP00000355658.2	Q9Y577-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461860 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727238

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111998

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	13
DANN	Benign	0.91
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.32
FATHMM_MKL	Benign	0.064	N
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.8	L
PhyloP100		0.017
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.24
Sift	Benign	0.54	T
Sift4G	Benign	0.38	T
Polyphen		0.99	D
Vest4		0.22
MutPred		0.44		Loss of catalytic residue at E413 (P = 0.0145)
MVP		0.76
MPC		0.38
ClinPred		0.21	T
GERP RS		3.0
Varity_R		0.061
gMVP		0.33
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs1194942172; hg19: chr1-228596097;