11-89870698-C-G

Variant names:

• chr11-89870698-C-G
• rs564890926
• NM_001164397.3:c.1273G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001164397.3(TRIM64B):​c.1273G>C​(p.Gly425Arg) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G425S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM64B NM_001164397.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.27
• Publications: 0 publications found

Genes affected

TRIM64B (HGNC:37147): (tripartite motif containing 64B) 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13389829).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164397.3. 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
	TRIM64B	NM_001164397.3	MANE Select	c.1273G>C	p.Gly425Arg	missense	Exon 7 of 7	NP_001157869.1	A6NI03

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM64B	ENST00000329862.7	TSL:1 MANE Select	c.1273G>C	p.Gly425Arg	missense	Exon 7 of 7	ENSP00000332969.6	A6NI03

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.15e-7 AC: 1 AN: 1398940 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689984

⚠️ 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: 31574

American (AMR) AF: 0.00 AC: 0 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25178

East Asian (EAS) AF: 0.00 AC: 0 AN: 35670

South Asian (SAS) AF: 0.00 AC: 0 AN: 79214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49284

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5560

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078808

Other (OTH) AF: 0.00 AC: 0 AN: 57956

⚠️ 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.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.34
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.44
DANN	Uncertain	0.98
DEOGEN2	Benign	0.013	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.6	L
PhyloP100		-1.3
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.053
Sift	Benign	0.11	T
Sift4G	Benign	0.22	T
Vest4		0.071
MutPred		0.68		Loss of ubiquitination at K424 (P = 0.0618)
MVP		0.076
ClinPred		0.14	T
GERP RS		-2.5
Varity_R		0.061
gMVP		0.054
Mutation Taster		=95/5	polymorphism

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

dbSNP: rs564890926; hg19: chr11-89603866;