1-228413805-C-T

Position:

• chr1-228413805-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_016102.4(TRIM17):​c.517G>A​(p.Glu173Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00239 in 1,614,080 control chromosomes in the GnomAD database, including 99 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (50 hom., cov: 33)
  • Exomes 𝑓: 0.0013 (49 hom.)
• Consequence: TRIM17 NM_016102.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.377

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.002860099).
• BP6: Variant 1-228413805-C-T is Benign according to our data. Variant chr1-228413805-C-T is described in ClinVar as [Benign]. Clinvar id is 769554.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0124 (1895/152338) while in subpopulation AFR AF= 0.0428 (1779/41562). AF 95% confidence interval is 0.0411. There are 50 homozygotes in gnomad4. There are 874 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM17	NM_016102.4	c.517G>A	p.Glu173Lys	missense_variant	3/7	ENST00000366698.7	NP_057186.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM17	ENST00000366698.7	c.517G>A	p.Glu173Lys	missense_variant	3/7	1	NM_016102.4	ENSP00000355659	P1
	ENST00000701501.1	n.283+6327C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.0124 AC: 1891 AN: 152220 Hom.: 50 Cov.: 33

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00556

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00716

GnomAD3 exomes AF: 0.00332 AC: 835 AN: 251252 Hom.: 15 AF XY: 0.00242 AC XY: 329 AN XY: 135840

Gnomad AFR exome AF: 0.0458

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000163

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.000106

Gnomad OTH exome AF: 0.00147

GnomAD4 exome AF: 0.00134 AC: 1960 AN: 1461742 Hom.: 49 Cov.: 31 AF XY: 0.00115 AC XY: 837 AN XY: 727192

Gnomad4 AFR exome AF: 0.0474

Gnomad4 AMR exome AF: 0.00215

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.0000549

Gnomad4 OTH exome AF: 0.00321

GnomAD4 genome AF: 0.0124 AC: 1895 AN: 152338 Hom.: 50 Cov.: 33 AF XY: 0.0117 AC XY: 874 AN XY: 74500

Gnomad4 AFR AF: 0.0428

Gnomad4 AMR AF: 0.00555

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00709

Alfa AF: 0.00251 Hom.: 16

Bravo AF: 0.0141

ESP6500AA AF: 0.0438 AC: 193

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00404 AC: 490

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 19, 2017	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.097
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	11
DANN	Benign	0.66
DEOGEN2	Benign	0.14	T;T;T;.;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.034	N
MetaRNN	Benign	0.0029	T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M;M;M;M;.;.
MutationTaster	Benign	1.0	N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	N;N;N;N;N;N
REVEL	Benign	0.059
Sift	Benign	0.67	T;T;T;T;T;T
Sift4G	Benign	0.79	T;T;T;T;.;.
Polyphen		0.0040	B;B;B;B;.;.
Vest4		0.24
MVP		0.27
MPC		0.27
ClinPred		0.0032	T
GERP RS		1.6
Varity_R		0.048
gMVP		0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs116188608; hg19: chr1-228601506;