1-228408434-A-C

Variant names:

• chr1-228408434-A-C
• rs142387185
• NM_016102.4:c.1201T>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016102.4(TRIM17):​c.1201T>G​(p.Ser401Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,172 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign 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. S401P) has been classified as Likely benign.

• Frequency: Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
• Consequence: TRIM17 NM_016102.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.820
• Publications: 1 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.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.049583554).

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.1201T>G	p.Ser401Ala	missense	Exon 7 of 7	NP_057186.1	Q9Y577-1
	TRIM17	NM_001024940.3		c.1201T>G	p.Ser401Ala	missense	Exon 7 of 7	NP_001020111.1	Q9Y577-1
	TRIM17	NM_001438323.1		c.1120T>G	p.Ser374Ala	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.1201T>G	p.Ser401Ala	missense	Exon 7 of 7	ENSP00000355659.2	Q9Y577-1
	TRIM17	ENST00000295033.7	TSL:1	c.1201T>G	p.Ser401Ala	missense	Exon 7 of 7	ENSP00000295033.3	Q9Y577-1
	TRIM17	ENST00000366697.6	TSL:2	c.1201T>G	p.Ser401Ala	missense	Exon 6 of 6	ENSP00000355658.2	Q9Y577-1

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 31

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152172 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74322

African (AFR) AF: 0.00 AC: 0 AN: 41438

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68024

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	0.10
DANN	Benign	0.30
DEOGEN2	Benign	0.087	T
Eigen	Benign	-1.9
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.045	N
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	-1.4	N
PhyloP100		0.82
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.58	N
REVEL	Benign	0.099
Sift	Benign	1.0	T
Sift4G	Benign	0.79	T
Polyphen		0.0010	B
Vest4		0.012
MutPred		0.56		Loss of methylation at K398 (P = 0.0673)
MVP		0.26
MPC		0.20
ClinPred		0.096	T
GERP RS		-6.4
Varity_R		0.049
gMVP		0.24
Mutation Taster		=98/2	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: rs142387185; hg19: chr1-228596135;