rs756662525

Variant names:

• chr11-89870918-G-T
• rs756662525
• NM_001164397.3:c.1053C>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001164397.3(TRIM64B):​c.1053C>A​(p.Asn351Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000592 in 152,106 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000060 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM64B NM_001164397.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -4.13
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.051578373).

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.1053C>A	p.Asn351Lys	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.1053C>A	p.Asn351Lys	missense	Exon 7 of 7	ENSP00000332969.6	A6NI03

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152106 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000399 AC: 63 AN: 157818 AF XY: 0.000360

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00158

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00403

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000600 AC: 84 AN: 1399342 Hom.: 0 Cov.: 31 AF XY: 0.0000594 AC XY: 41 AN XY: 690156

⚠️ 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: 31496

American (AMR) AF: 0.00185 AC: 66 AN: 35680

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 35658

South Asian (SAS) AF: 0.000164 AC: 13 AN: 79210

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5666

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078894

Other (OTH) AF: 0.0000861 AC: 5 AN: 58082

⚠️ 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 AF: 0.0000592 AC: 9 AN: 152106 Hom.: 0 Cov.: 30 AF XY: 0.0000404 AC XY: 3 AN XY: 74308

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

African (AFR) AF: 0.00 AC: 0 AN: 41354

American (AMR) AF: 0.000589 AC: 9 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68054

Other (OTH) AF: 0.00 AC: 0 AN: 2090

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000480 Hom.: 0

ExAC AF: 0.000191 AC: 5

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	Uncertain	0.56
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	8.5
DANN	Uncertain	0.98
DEOGEN2	Benign	0.077	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0066	N
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L
PhyloP100		-4.1
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.095
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.033	D
Vest4		0.10
MutPred		0.76		Gain of methylation at N351 (P = 0.0221)
MVP		0.048
ClinPred		0.12	T
GERP RS		-4.2
Varity_R		0.32
gMVP		0.018
Mutation Taster		=100/0	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: rs756662525; hg19: chr11-89604086;