rs371493682

Variant names:

• chr1-228408725-C-A
• rs371493682
• NM_016102.4:c.910G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-228408725-C-A
• chr1-228408725-C-T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_016102.4(TRIM17):​c.910G>T​(p.Ala304Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000187 in 1,602,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A304T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: TRIM17 NM_016102.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.98
• 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_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.969

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.910G>T	p.Ala304Ser	missense	Exon 7 of 7	NP_057186.1	Q9Y577-1
	TRIM17	NM_001024940.3		c.910G>T	p.Ala304Ser	missense	Exon 7 of 7	NP_001020111.1	Q9Y577-1
	TRIM17	NM_001438323.1		c.829G>T	p.Ala277Ser	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.910G>T	p.Ala304Ser	missense	Exon 7 of 7	ENSP00000355659.2	Q9Y577-1
	TRIM17	ENST00000295033.7	TSL:1	c.910G>T	p.Ala304Ser	missense	Exon 7 of 7	ENSP00000295033.3	Q9Y577-1
	TRIM17	ENST00000456946.6	TSL:1	c.*298G>T		3_prime_UTR	Exon 6 of 6	ENSP00000403312.2	Q9Y577-2

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152146 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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1450806 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 722078

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.00 AC: 0 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42714

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5736

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111820

Other (OTH) AF: 0.0000166 AC: 1 AN: 60308

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152146 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74326

African (AFR) AF: 0.0000241 AC: 1 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

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

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.090	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.55	D
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.042	D
MetaRNN	Pathogenic	0.97	D
MetaSVM	Uncertain	0.074	D
MutationAssessor	Pathogenic	3.2	M
PhyloP100		7.0
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.8	D
REVEL	Uncertain	0.54
Sift	Uncertain	0.018	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.86		Gain of disorder (P = 0.0715)
MVP		0.84
MPC		0.82
ClinPred		0.99	D
GERP RS		4.7
Varity_R		0.20
gMVP		0.34
Mutation Taster		=84/16	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs371493682; hg19: chr1-228596426;