rs1182818518

Variant names:

• chr11-49054157-C-T
• rs1182818518
• NM_001206631.1:c.910G>A

Variant summary

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

The NM_001206631.1(TRIM64C):​c.910G>A​(p.Glu304Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000357 in 1,399,262 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000036 (0 hom.)
• Consequence: TRIM64C NM_001206631.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.11
• Publications: 0 publications found

Genes affected

TRIM64C (HGNC:37148): (tripartite motif containing 64C) 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=0.1589047).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206631.1. 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
	TRIM64C	NM_001206631.1	MANE Select	c.910G>A	p.Glu304Lys	missense	Exon 6 of 6	NP_001193560.1	A6NLI5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM64C	ENST00000617704.1	TSL:5 MANE Select	c.910G>A	p.Glu304Lys	missense	Exon 6 of 6	ENSP00000481815.1	A6NLI5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000320 AC: 5 AN: 156392 AF XY: 0.0000121

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000202

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: 0.00

GnomAD4 exome AF: 0.00000357 AC: 5 AN: 1399262 Hom.: 0 Cov.: 34 AF XY: 0.00000145 AC XY: 1 AN XY: 690156

African (AFR) AF: 0.00 AC: 0 AN: 31590

American (AMR) AF: 0.000140 AC: 5 AN: 35696

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 35738

South Asian (SAS) AF: 0.00 AC: 0 AN: 79228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49306

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078812

Other (OTH) AF: 0.00 AC: 0 AN: 58020

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000843 Hom.: 0

Bravo AF: 0.00000756

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	0.079
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	10
DANN	Uncertain	0.98
Eigen	Benign	-0.34
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-1.0	T
PhyloP100		1.1
PrimateAI	Uncertain	0.54	T
Sift4G	Benign	0.15	T
Vest4		0.19
MVP		0.17
ClinPred		0.11	T
GERP RS		1.3
Varity_R		0.039
gMVP		0.18
Mutation Taster		=98/2	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1182818518; hg19: chr11-49075709;