4-165041160-T-C

Position:

• chr4-165041160-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_152620.3(TRIM60):​c.1088T>C​(p.Ile363Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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)
• Consequence: TRIM60 NM_152620.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.44

Genes affected

TRIM60 (HGNC:21162): (tripartite motif containing 60) The protein encoded by this gene contains a RING finger domain, a motif present in a variety of functionally distinct proteins and known to be involved in protein-protein and protein-DNA interactions. Pseudogenes of this gene are located on more than six chromosomes including chromosome 4. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03547436).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM60	NM_152620.3	c.1088T>C	p.Ile363Thr	missense_variant	3/3	ENST00000512596.6
TRIM60	NM_001258025.2	c.1088T>C	p.Ile363Thr	missense_variant	4/4
TRIM60	XM_011531683.3	c.1088T>C	p.Ile363Thr	missense_variant	2/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM60	ENST00000512596.6	c.1088T>C	p.Ile363Thr	missense_variant	3/3	2	NM_152620.3	P1
TRIM60	ENST00000508504.1	c.1088T>C	p.Ile363Thr	missense_variant	3/3	1		P1
TRIM60	ENST00000341062.6	c.1088T>C	p.Ile363Thr	missense_variant	2/2	5		P1
TRIM60	ENST00000647760.1	c.1088T>C	p.Ile363Thr	missense_variant	4/4			P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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

Mar 13, 2023

The c.1088T>C (p.I363T) alteration is located in exon 3 (coding exon 1) of the TRIM60 gene. This alteration results from a T to C substitution at nucleotide position 1088, causing the isoleucine (I) at amino acid position 363 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	0.17
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	3.4
DANN	Benign	0.74
DEOGEN2	Benign	0.0061	T;T;T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0037	N
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.035	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.12	N;N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.38	T
Polyphen		0.0010	B;B;B;B
Vest4		0.035, 0.031, 0.034
MutPred		0.54		Loss of stability (P = 0.0277);Loss of stability (P = 0.0277);Loss of stability (P = 0.0277);Loss of stability (P = 0.0277);
MVP		0.030
MPC		0.046
ClinPred		0.063	T
GERP RS		-0.38
Varity_R		0.036
gMVP		0.036

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-165962312;