11-55265042-C-T

Variant names:

• chr11-55265042-C-T
• rs201031596
• NM_024114.5:c.187C>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024114.5(TRIM48):​c.187C>T​(p.Pro63Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000726 in 1,584,046 control chromosomes in the GnomAD database, including 9 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. P63T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000034 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000077 (9 hom.)
• Consequence: TRIM48 NM_024114.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.569
• Publications: 1 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03376451).
• BS2: High Homozygotes in GnomAdExome4 at 9 AR gene

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.187C>T	p.Pro63Ser	missense	Exon 2 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.187C>T	p.Pro63Ser	missense	Exon 2 of 6	ENSP00000402414.2	Q8IWZ4

Frequencies

GnomAD3 genomes AF: 0.0000338 AC: 5 AN: 147886 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.0000248

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000598

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000285 AC: 7 AN: 245378 AF XY: 0.0000302

Gnomad AFR exome AF: 0.00

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: 0.0000624

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000766 AC: 110 AN: 1436046 Hom.: 9 Cov.: 32 AF XY: 0.0000743 AC XY: 53 AN XY: 713382

African (AFR) AF: 0.00 AC: 0 AN: 33158

American (AMR) AF: 0.00 AC: 0 AN: 43876

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25786

East Asian (EAS) AF: 0.00 AC: 0 AN: 36812

South Asian (SAS) AF: 0.00 AC: 0 AN: 79576

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53222

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5092

European-Non Finnish (NFE) AF: 0.000100 AC: 110 AN: 1099290

Other (OTH) AF: 0.00 AC: 0 AN: 59234

GnomAD4 genome AF: 0.0000338 AC: 5 AN: 148000 Hom.: 0 Cov.: 30 AF XY: 0.0000277 AC XY: 2 AN XY: 72144

African (AFR) AF: 0.0000247 AC: 1 AN: 40502

American (AMR) AF: 0.00 AC: 0 AN: 14698

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3426

East Asian (EAS) AF: 0.00 AC: 0 AN: 4614

South Asian (SAS) AF: 0.00 AC: 0 AN: 4146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10486

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000598 AC: 4 AN: 66892

Other (OTH) AF: 0.00 AC: 0 AN: 2046

Alfa AF: 0.000113 Hom.: 0

Bravo AF: 0.0000416

ExAC AF: 0.00000839 AC: 1

EpiCase AF: 0.0000551

EpiControl AF: 0.000180

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	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	1.5
DANN	Benign	0.34
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0017	N
M_CAP	Benign	0.0057	T
MetaRNN	Benign	0.034	T
MetaSVM	Benign	-0.88	T
PhyloP100		-0.57
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.20
Sift	Benign	0.38	T
Sift4G	Benign	0.25	T
Vest4		0.13
MVP		0.15
MPC		0.0031
ClinPred		0.027	T
GERP RS		-1.2
gMVP		0.020
Mutation Taster		=99/1	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: rs201031596; hg19: chr11-55032518; COSMIC: COSV101338256; COSMIC: COSV101338256;