17-18734919-A-G

Position:

• chr17-18734919-A-G

Variant summary

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

The ENST00000571708.5(TRIM16L):​n.1132A>G variant causes a non coding transcript exon change. The variant allele was found at a frequency of 0.00000205 in 1,460,154 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: TRIM16L ENST00000571708.5 non_coding_transcript_exon
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.73

Genes affected

TRIM16L (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM16L	NR_172633.1	n.1212A>G		non_coding_transcript_exon_variant	10/10
TRIM16L	NR_172634.1	n.1061A>G		non_coding_transcript_exon_variant	9/9
TRIM16L	NR_172635.1	n.963A>G		non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM16L	ENST00000571708.5	n.1132A>G		non_coding_transcript_exon_variant	10/10	1
TRIM16L	ENST00000414850.6	n.491A>G		non_coding_transcript_exon_variant	3/3	2
TRIM16L	ENST00000424146.2	n.585A>G		non_coding_transcript_exon_variant	4/4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1460154 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726150

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

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 12, 2022

The c.506A>G (p.Y169C) alteration is located in exon 5 (coding exon 4) of the TRIM16L gene. This alteration results from a A to G substitution at nucleotide position 506, causing the tyrosine (Y) at amino acid position 169 to be replaced by a cysteine (C). 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	Pathogenic	0.71
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.19
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.0023	T
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L
PrimateAI	Pathogenic	0.85	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.12
Sift	Benign	0.062	T
Sift4G	Uncertain	0.012	D
Polyphen		1.0	D
Vest4		0.55
MutPred		0.39		Gain of methylation at K168 (P = 0.0211);
MVP		0.31
ClinPred		0.77	D
GERP RS		3.5
Varity_R		0.22
gMVP		0.43

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: rs1350880182; hg19: chr17-18638232;