11-89973453-T-G

Variant names:

• chr11-89973453-T-G
• NM_001136486.2:c.914T>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001136486.2(TRIM64):​c.914T>G​(p.Val305Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 8/13 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)
  • Exomes 𝑓: 0.0000061 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM64 NM_001136486.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0200

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.11000967).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM64	NM_001136486.2	c.914T>G	p.Val305Gly	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.914T>G	p.Val305Gly	missense_variant	Exon 7 of 7	1	NM_001136486.2	ENSP00000483764.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000611 AC: 2 AN: 327296 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 166908

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000843

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.914T>G (p.V305G) alteration is located in exon 6 (coding exon 6) of the TRIM64 gene. This alteration results from a T to G substitution at nucleotide position 914, causing the valine (V) at amino acid position 305 to be replaced by a glycine (G). 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	0.12
BayesDel_addAF	Benign	-0.094	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	4.8
DANN	Benign	0.48
DEOGEN2	Benign	0.088	T
FATHMM_MKL	Benign	0.0022	N
LIST_S2	Benign	0.35	T
MetaRNN	Benign	0.11	T
MutationAssessor	Uncertain	2.6	M
PrimateAI	Uncertain	0.53	T
Sift4G	Benign	0.091	T
Polyphen		0.41	B
Vest4		0.095
MVP		0.22
GERP RS		-2.0
Varity_R		0.047
gMVP		0.018

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: chr11-89706621;