chr11-89973453-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001136486.2. 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
	TRIM64	NM_001136486.2	MANE Select	c.914T>G	p.Val305Gly	missense	Exon 7 of 7	NP_001129958.1	A6NGJ6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM64	ENST00000533122.4	TSL:1 MANE Select	c.914T>G	p.Val305Gly	missense	Exon 7 of 7	ENSP00000483764.1	A6NGJ6

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 4790

American (AMR) AF: 0.00 AC: 0 AN: 8048

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 8042

East Asian (EAS) AF: 0.00 AC: 0 AN: 10366

South Asian (SAS) AF: 0.00 AC: 0 AN: 21816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20996

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1048

European-Non Finnish (NFE) AF: 0.00000843 AC: 2 AN: 237116

Other (OTH) AF: 0.00 AC: 0 AN: 15074

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

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	0.12
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
PhyloP100		0.020
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

Other links and lift over

hg19: chr11-89706621;