chr17-18732068-G-A

Position:

• chr17-18732068-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000571708.5(TRIM16L):​n.1023G>A variant causes a non coding transcript exon change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: TRIM16L ENST00000571708.5 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.97

Genes affected

TRIM16L (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15200159).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM16L	NR_172633.1	n.1103G>A		non_coding_transcript_exon_variant	9/10
TRIM16L	NR_172634.1	n.952G>A		non_coding_transcript_exon_variant	8/9
TRIM16L	NR_172635.1	n.854G>A		non_coding_transcript_exon_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM16L	ENST00000571708.5	n.1023G>A		non_coding_transcript_exon_variant	9/10	1
TRIM16L	ENST00000424146.2	n.476G>A		non_coding_transcript_exon_variant	3/4	3
TRIM16L	ENST00000449552.6	n.1881G>A		non_coding_transcript_exon_variant	6/7	2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2023

The c.397G>A (p.A133T) alteration is located in exon 4 (coding exon 3) of the TRIM16L gene. This alteration results from a G to A substitution at nucleotide position 397, causing the alanine (A) at amino acid position 133 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.053	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	17
DANN	Benign	0.81
DEOGEN2	Benign	0.0079	T
Eigen	Benign	0.0093
Eigen_PC	Benign	0.0040
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.60	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.25	N
REVEL	Benign	0.082
Sift	Benign	0.43	T
Sift4G	Benign	0.15	T
Polyphen		0.57	P
Vest4		0.11
MutPred		0.35		Gain of phosphorylation at A133 (P = 0.06);
MVP		0.59
ClinPred		0.45	T
GERP RS		3.3
Varity_R		0.061
gMVP		0.26

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: rs2034684115; hg19: chr17-18635381;