chr17-75891246-C-T

Variant names:

• chr17-75891246-C-T
• rs2065261618
• NM_173547.4:c.1087G>A

Variant summary

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

The NM_173547.4(TRIM65):​c.1087G>A​(p.Gly363Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,460,606 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: TRIM65 NM_173547.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.966
• Publications: 0 publications found

Genes affected

TRIM65 (HGNC:27316): (tripartite motif containing 65) Predicted to enable zinc ion binding activity. Involved in positive regulation of autophagy. Located in cytosol and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

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=0.052619696).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173547.4. 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
	TRIM65	NM_173547.4	MANE Select	c.1087G>A	p.Gly363Ser	missense	Exon 6 of 6	NP_775818.2
	TRIM65	NM_001256124.2		c.1021G>A	p.Gly341Ser	missense	Exon 5 of 5	NP_001243053.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM65	ENST00000269383.8	TSL:1 MANE Select	c.1087G>A	p.Gly363Ser	missense	Exon 6 of 6	ENSP00000269383.3	Q6PJ69
	TRIM65	ENST00000924710.1		c.1126G>A	p.Gly376Ser	missense	Exon 6 of 6	ENSP00000594769.1
	TRIM65	ENST00000924711.1		c.1060G>A	p.Gly354Ser	missense	Exon 5 of 5	ENSP00000594770.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1460606 Hom.: 0 Cov.: 33 AF XY: 0.00000826 AC XY: 6 AN XY: 726628

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52432

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5768

European-Non Finnish (NFE) AF: 0.00000810 AC: 9 AN: 1111734

Other (OTH) AF: 0.00 AC: 0 AN: 60378

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	12
DANN	Benign	0.61
DEOGEN2	Benign	0.00062	T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.66
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.40	N
PhyloP100		0.97
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.096
Sift	Benign	0.70	T
Sift4G	Benign	0.46	T
Polyphen		0.012	B
Vest4		0.088
MutPred		0.28		Gain of glycosylation at G363 (P = 0.0081)
MVP		0.38
MPC		0.18
ClinPred		0.082	T
GERP RS		4.2
Varity_R		0.15
gMVP		0.23
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2065261618; hg19: chr17-73887327;