11-55262287-T-A

Variant names:

• chr11-55262287-T-A
• rs1035934795
• NM_024114.5:c.20T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_024114.5(TRIM48):​c.20T>A​(p.Val7Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,548,738 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V7A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: TRIM48 NM_024114.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.383
• Publications: 0 publications found

Genes affected

TRIM48 (HGNC:19021): (tripartite motif containing 48) 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=0.09537554).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024114.5. 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
	TRIM48	NM_024114.5	MANE Select	c.20T>A	p.Val7Glu	missense	Exon 1 of 6	NP_077019.2	Q8IWZ4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM48	ENST00000417545.5	TSL:1 MANE Select	c.20T>A	p.Val7Glu	missense	Exon 1 of 6	ENSP00000402414.2	Q8IWZ4

Frequencies

GnomAD3 genomes AF: 0.000145 AC: 22 AN: 152174 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000458

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000256 AC: 4 AN: 156166 AF XY: 0.0000362

Gnomad AFR exome AF: 0.000506

Gnomad AMR exome AF: 0.00

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: 0.0000186 AC: 26 AN: 1396564 Hom.: 0 Cov.: 29 AF XY: 0.0000203 AC XY: 14 AN XY: 688830

African (AFR) AF: 0.000730 AC: 23 AN: 31488

American (AMR) AF: 0.00 AC: 0 AN: 35688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25158

East Asian (EAS) AF: 0.00 AC: 0 AN: 35712

South Asian (SAS) AF: 0.00 AC: 0 AN: 79136

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49270

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4062

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078270

Other (OTH) AF: 0.0000519 AC: 3 AN: 57780

GnomAD4 genome AF: 0.000145 AC: 22 AN: 152174 Hom.: 1 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74326

African (AFR) AF: 0.000458 AC: 19 AN: 41460

American (AMR) AF: 0.000131 AC: 2 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68032

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

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000132

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	0.13
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	2.8
DANN	Benign	0.83
Eigen	Benign	-0.82
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0020	N
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.79	T
PhyloP100		0.38
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.053
Sift	Uncertain	0.0040	D
Sift4G	Pathogenic	0.0	D
Vest4		0.40
MutPred		0.43		Gain of disorder (P = 0.0023)
MVP		0.24
MPC		0.0039
ClinPred		0.064	T
GERP RS		-0.82
PromoterAI		0.0040	Neutral
gMVP		0.17
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: rs1035934795; hg19: chr11-55029763;