chr1-228409210-C-G

Variant names:

• chr1-228409210-C-G
• rs373119420
• NM_016102.4:c.845G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016102.4(TRIM17):​c.845G>C​(p.Arg282Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,613,968 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R282G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00013 (1 hom.)
• Consequence: TRIM17 NM_016102.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.495
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.22965166).

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.845G>C	p.Arg282Thr	missense	Exon 6 of 7	NP_057186.1	Q9Y577-1
	TRIM17	NM_001024940.3		c.845G>C	p.Arg282Thr	missense	Exon 6 of 7	NP_001020111.1	Q9Y577-1
	TRIM17	NM_001438323.1		c.764G>C	p.Arg255Thr	missense	Exon 6 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.845G>C	p.Arg282Thr	missense	Exon 6 of 7	ENSP00000355659.2	Q9Y577-1
	TRIM17	ENST00000295033.7	TSL:1	c.845G>C	p.Arg282Thr	missense	Exon 6 of 7	ENSP00000295033.3	Q9Y577-1
	TRIM17	ENST00000456946.6	TSL:1	c.845G>C	p.Arg282Thr	missense	Exon 6 of 6	ENSP00000403312.2	Q9Y577-2

Frequencies

GnomAD3 genomes AF: 0.0000460 AC: 7 AN: 152100 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000517 AC: 13 AN: 251452 AF XY: 0.0000589

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000114

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000131 AC: 191 AN: 1461868 Hom.: 1 Cov.: 31 AF XY: 0.000116 AC XY: 84 AN XY: 727244

African (AFR) AF: 0.0000299 AC: 1 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

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

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

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.000168 AC: 187 AN: 1112004

Other (OTH) AF: 0.0000331 AC: 2 AN: 60394

GnomAD4 genome AF: 0.0000460 AC: 7 AN: 152100 Hom.: 0 Cov.: 31 AF XY: 0.0000404 AC XY: 3 AN XY: 74288

African (AFR) AF: 0.0000241 AC: 1 AN: 41416

American (AMR) AF: 0.00 AC: 0 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.0000564 Hom.: 0

Bravo AF: 0.0000378

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.0000330 AC: 4

EpiCase AF: 0.00

EpiControl AF: 0.000237

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	0.22
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.0053
Eigen_PC	Benign	-0.049
FATHMM_MKL	Benign	0.59	D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.49
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.12
Sift	Uncertain	0.011	D
Sift4G	Uncertain	0.035	D
Polyphen		0.65	P
Vest4		0.49
MVP		0.66
MPC		0.75
ClinPred		0.32	T
GERP RS		2.4
Varity_R		0.096
gMVP		0.30
Mutation Taster		=92/8	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs373119420; hg19: chr1-228596911;