1-228408239-T-G

Variant names:

• chr1-228408239-T-G
• rs1335170214
• NM_016102.4:c.1396A>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.1396A>C​(p.Met466Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000321 in 1,559,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 31)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: TRIM17 NM_016102.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.649
• 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=0.07501745).

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.1396A>C	p.Met466Leu	missense	Exon 7 of 7	NP_057186.1	Q9Y577-1
	TRIM17	NM_001024940.3		c.1396A>C	p.Met466Leu	missense	Exon 7 of 7	NP_001020111.1	Q9Y577-1
	TRIM17	NM_001438323.1		c.1315A>C	p.Met439Leu	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.1396A>C	p.Met466Leu	missense	Exon 7 of 7	ENSP00000355659.2	Q9Y577-1
	TRIM17	ENST00000295033.7	TSL:1	c.1396A>C	p.Met466Leu	missense	Exon 7 of 7	ENSP00000295033.3	Q9Y577-1
	TRIM17	ENST00000366697.6	TSL:2	c.1396A>C	p.Met466Leu	missense	Exon 6 of 6	ENSP00000355658.2	Q9Y577-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152094 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome AF: 7.10e-7 AC: 1 AN: 1407558 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 694380

African (AFR) AF: 0.0000313 AC: 1 AN: 31940

American (AMR) AF: 0.00 AC: 0 AN: 38364

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21882

East Asian (EAS) AF: 0.00 AC: 0 AN: 39366

South Asian (SAS) AF: 0.00 AC: 0 AN: 76564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50878

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5454

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1085146

Other (OTH) AF: 0.00 AC: 0 AN: 57964

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152094 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74278

African (AFR) AF: 0.0000966 AC: 4 AN: 41408

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000151

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	0.27
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Benign	0.76
DEOGEN2	Benign	0.077	T
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.18
FATHMM_MKL	Uncertain	0.82	D
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	-0.26	N
PhyloP100		0.65
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	0.17	N
REVEL	Benign	0.12
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.13	B
Vest4		0.19
MutPred		0.58		Gain of sheet (P = 0.0344)
MVP		0.47
MPC		0.83
ClinPred		0.46	T
GERP RS		4.8
Varity_R		0.31
gMVP		0.27
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs1335170214; hg19: chr1-228595940;