11-49032366-T-C

Variant names:

• chr11-49032366-T-C
• rs771251284
• NM_001206626.2:c.502T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001206626.2(TRIM49B):​c.502T>C​(p.Trp168Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. W168G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: TRIM49B NM_001206626.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.13
• Publications: 1 publications found

Genes affected

TRIM49B (HGNC:42955): (tripartite motif containing 49B)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206626.2. 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
	TRIM49B	NM_001206626.2	MANE Select	c.502T>C	p.Trp168Arg	missense	Exon 3 of 7	NP_001193555.1	A6NDI0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM49B	ENST00000332682.9	TSL:1 MANE Select	c.502T>C	p.Trp168Arg	missense	Exon 3 of 7	ENSP00000330216.7	A6NDI0
	TRIM49B	ENST00000622138.4	TSL:1	c.502T>C	p.Trp168Arg	missense	Exon 4 of 8	ENSP00000481457.1	A6NDI0

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000419 AC: 1 AN: 238810 AF XY: 0.00

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: 0.00000938

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461088 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 726898

African (AFR) AF: 0.00 AC: 0 AN: 33386

American (AMR) AF: 0.00 AC: 0 AN: 44596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86214

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5722

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111642

Other (OTH) AF: 0.0000166 AC: 1 AN: 60326

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.00000826 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	14
DANN	Benign	0.46
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.0075	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0017	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Pathogenic	3.3	M
PhyloP100		1.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Pathogenic	-11	D
REVEL	Benign	0.066
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0060	D
Vest4		0.54
MutPred		0.49		Gain of disorder (P = 0.0056)
MVP		0.28
MPC		4.9
ClinPred		0.43	T
GERP RS		0.11
Varity_R		0.51
gMVP		0.28
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: rs771251284; hg19: chr11-49053918; COSMIC: COSV60320847;