11-89973807-C-T

Variant names:

• chr11-89973807-C-T
• NM_001136486.2:c.1268C>T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001136486.2(TRIM64):​c.1268C>T​(p.Ser423Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: TRIM64 NM_001136486.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -9.37

Genes affected

TRIM64 (HGNC:14663): (tripartite motif containing 64) Predicted to enable ubiquitin protein ligase activity. Predicted to be involved in innate immune response; protein ubiquitination; and regulation of gene expression. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.051582426).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM64	NM_001136486.2	c.1268C>T	p.Ser423Phe	missense_variant	Exon 7 of 7	ENST00000533122.4	NP_001129958.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM64	ENST00000533122.4	c.1268C>T	p.Ser423Phe	missense_variant	Exon 7 of 7	1	NM_001136486.2	ENSP00000483764.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 05, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1268C>T (p.S423F) alteration is located in exon 6 (coding exon 6) of the TRIM64 gene. This alteration results from a C to T substitution at nucleotide position 1268, causing the serine (S) at amino acid position 423 to be replaced by a phenylalanine (F). 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	0.21
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	0.0030
DANN	Benign	0.43
DEOGEN2	Benign	0.043	T
FATHMM_MKL	Benign	0.0010	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.052	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.66	T
Sift4G	Benign	0.58	T
Polyphen		0.024	B
Vest4		0.12
MVP		0.15
GERP RS		-2.8
Varity_R		0.055
gMVP		0.010

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: chr11-89706975;