11-89798233-G-C

Variant names:

• chr11-89798233-G-C
• rs758579239
• NM_020358.2:c.1256C>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.1256C>G​(p.Thr419Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T419N) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000098 (0 hom., cov: 17)
  • Exomes 𝑓: 0.00020 (3 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM49 NM_020358.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.86
• 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=0.024606168).

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.1256C>G	p.Thr419Ser	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.1256C>G	p.Thr419Ser	missense	Exon 8 of 8	ENSP00000327604.1	P0CI25
	TRIM49	ENST00000532501.2	TSL:5	c.1025C>G	p.Thr342Ser	missense	Exon 6 of 6	ENSP00000431618.2	E9PK69

Frequencies

GnomAD3 genomes AF: 0.0000979 AC: 12 AN: 122550 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000176

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00235

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000166

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000455 AC: 106 AN: 233148 AF XY: 0.000543

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000451

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000187

Gnomad OTH exome AF: 0.000173

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000197 AC: 285 AN: 1443990 Hom.: 3 Cov.: 30 AF XY: 0.000246 AC XY: 177 AN XY: 718242

African (AFR) AF: 0.00 AC: 0 AN: 31734

American (AMR) AF: 0.000278 AC: 12 AN: 43226

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25854

East Asian (EAS) AF: 0.00 AC: 0 AN: 36652

South Asian (SAS) AF: 0.00266 AC: 227 AN: 85494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5632

European-Non Finnish (NFE) AF: 0.0000344 AC: 38 AN: 1104038

Other (OTH) AF: 0.000134 AC: 8 AN: 59594

GnomAD4 genome AF: 0.0000979 AC: 12 AN: 122632 Hom.: 0 Cov.: 17 AF XY: 0.000153 AC XY: 9 AN XY: 58732

African (AFR) AF: 0.00 AC: 0 AN: 29164

American (AMR) AF: 0.000176 AC: 2 AN: 11394

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3152

East Asian (EAS) AF: 0.00 AC: 0 AN: 3798

South Asian (SAS) AF: 0.00234 AC: 9 AN: 3838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8232

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 266

European-Non Finnish (NFE) AF: 0.0000166 AC: 1 AN: 60390

Other (OTH) AF: 0.00 AC: 0 AN: 1678

Alfa AF: 0.0000480 Hom.: 0

ExAC AF: 0.000405 AC: 48

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	0.054
DANN	Benign	0.23
DEOGEN2	Benign	0.0068	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0016	N
LIST_S2	Benign	0.081	T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.025	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	1.9	L
PhyloP100		-1.9
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.77	N
REVEL	Benign	0.078
Sift	Benign	0.86	T
Sift4G	Benign	0.76	T
Polyphen		0.0010	B
Vest4		0.056
MutPred		0.46		Loss of ubiquitination at K418 (P = 0.1099)
MVP		0.093
MPC		1.1
ClinPred		0.017	T
GERP RS		-1.7
Varity_R		0.057
gMVP		0.037
Mutation Taster		=98/2	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: rs758579239; hg19: chr11-89531401;