NM_020358.2:c.1159A>G

Variant names:

• chr11-89798330-T-C
• rs1168642124
• NM_020358.2:c.1159A>G

Variant summary

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

The NM_020358.2(TRIM49):​c.1159A>G​(p.Ile387Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000133 in 1,573,212 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (1 hom., cov: 19)
  • Exomes 𝑓: 0.000013 (1 hom.)
• Consequence: TRIM49 NM_020358.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.26
• Publications: 0 publications found

Genes affected

TRIM49 (HGNC:13431): (tripartite motif containing 49) The protein encoded by this gene contains a RING zinc finger, a motif known to be involved in protein-protein interactions. This gene has been found to be preferentially expressed in testis. Related pseudogenes and gene duplicates have also been identified on chromosome 11. [provided by RefSeq, Aug 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.053181887).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020358.2. 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
	TRIM49	NM_020358.2	MANE Select	c.1159A>G	p.Ile387Val	missense	Exon 8 of 8	NP_065091.1	P0CI25

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM49	ENST00000329758.5	TSL:1 MANE Select	c.1159A>G	p.Ile387Val	missense	Exon 8 of 8	ENSP00000327604.1	P0CI25
	TRIM49	ENST00000532501.2	TSL:5	c.928A>G	p.Ile310Val	missense	Exon 6 of 6	ENSP00000431618.2	E9PK69

Frequencies

GnomAD3 genomes AF: 0.0000142 AC: 2 AN: 140960 Hom.: 1 Cov.: 19

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000442

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: 0.0000247 AC: 6 AN: 243324 AF XY: 0.00000758

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: 0.0000536

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000133 AC: 19 AN: 1432252 Hom.: 1 Cov.: 30 AF XY: 0.0000154 AC XY: 11 AN XY: 712854

African (AFR) AF: 0.00 AC: 0 AN: 30968

American (AMR) AF: 0.00 AC: 0 AN: 41410

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25780

East Asian (EAS) AF: 0.00 AC: 0 AN: 35758

South Asian (SAS) AF: 0.00 AC: 0 AN: 84836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51448

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5614

European-Non Finnish (NFE) AF: 0.0000173 AC: 19 AN: 1097358

Other (OTH) AF: 0.00 AC: 0 AN: 59080

GnomAD4 genome AF: 0.0000142 AC: 2 AN: 140960 Hom.: 1 Cov.: 19 AF XY: 0.00 AC XY: 0 AN XY: 68422

African (AFR) AF: 0.00 AC: 0 AN: 35918

American (AMR) AF: 0.00 AC: 0 AN: 13636

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3390

East Asian (EAS) AF: 0.000442 AC: 2 AN: 4522

South Asian (SAS) AF: 0.00 AC: 0 AN: 4542

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9690

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66202

Other (OTH) AF: 0.00 AC: 0 AN: 1960

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000113

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	0.083
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	0.013
DANN	Benign	0.20
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0028	N
LIST_S2	Benign	0.044	T
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.090	N
PhyloP100		-1.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.098
Sift	Benign	0.54	T
Sift4G	Benign	0.67	T
Polyphen		0.0010	B
Vest4		0.068
MutPred		0.56		Loss of sheet (P = 0.0181)
MVP		0.043
MPC		1.0
ClinPred		0.021	T
GERP RS		-2.1
Varity_R		0.020
gMVP		0.018
Mutation Taster		=93/7	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: rs1168642124; hg19: chr11-89531498;