NM_020358.2:c.902T>C

Variant names:

• chr11-89798587-A-G
• rs748454899
• NM_020358.2:c.902T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020358.2(TRIM49):​c.902T>C​(p.Phe301Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000258 in 1,549,838 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000077 (0 hom., cov: 21)
  • Exomes 𝑓: 0.0000021 (1 hom.)
• Consequence: TRIM49 NM_020358.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.31
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05426696).

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.902T>C	p.Phe301Ser	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.902T>C	p.Phe301Ser	missense	Exon 8 of 8	ENSP00000327604.1	P0CI25
	TRIM49	ENST00000532501.2	TSL:5	c.671T>C	p.Phe224Ser	missense	Exon 6 of 6	ENSP00000431618.2	E9PK69

Frequencies

GnomAD3 genomes AF: 0.00000766 AC: 1 AN: 130498 Hom.: 0 Cov.: 21

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000243

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: 0.00000830 AC: 2 AN: 240974 AF XY: 0.00000764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000116

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000211 AC: 3 AN: 1419340 Hom.: 1 Cov.: 62 AF XY: 0.00 AC XY: 0 AN XY: 706624

African (AFR) AF: 0.00 AC: 0 AN: 28950

American (AMR) AF: 0.00 AC: 0 AN: 40966

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25538

East Asian (EAS) AF: 0.0000843 AC: 3 AN: 35572

South Asian (SAS) AF: 0.00 AC: 0 AN: 83510

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50964

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5572

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1089726

Other (OTH) AF: 0.00 AC: 0 AN: 58542

GnomAD4 genome AF: 0.00000766 AC: 1 AN: 130498 Hom.: 0 Cov.: 21 AF XY: 0.0000158 AC XY: 1 AN XY: 63360

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29468

American (AMR) AF: 0.00 AC: 0 AN: 12810

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3318

East Asian (EAS) AF: 0.000243 AC: 1 AN: 4112

South Asian (SAS) AF: 0.00 AC: 0 AN: 4176

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 298

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 64570

Other (OTH) AF: 0.00 AC: 0 AN: 1812

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000832 AC: 1

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	0.16
BayesDel_addAF	Benign	-0.48	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	1.2
DANN	Benign	0.28
DEOGEN2	Benign	0.0031	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00080	N
LIST_S2	Benign	0.30	T
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.054	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	1.5	L
PhyloP100		-1.3
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.70	N
REVEL	Benign	0.029
Sift	Benign	0.44	T
Sift4G	Benign	0.43	T
Polyphen		0.049	B
Vest4		0.072
MutPred		0.56		Gain of disorder (P = 0.0103)
MVP		0.043
MPC		1.9
ClinPred		0.014	T
GERP RS		-0.99
Varity_R		0.051
gMVP		0.073
Mutation Taster		=96/4	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: rs748454899; hg19: chr11-89531755;