11-49032339-A-G

Position:

• chr11-49032339-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001206626.2(TRIM49B):​c.475A>G​(p.Asn159Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,270 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: TRIM49B NM_001206626.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.213

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18085545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TRIM49B	NM_001206626.2	c.475A>G	p.Asn159Asp	missense_variant	3/7	ENST00000332682.9	NP_001193555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TRIM49B	ENST00000332682.9	c.475A>G	p.Asn159Asp	missense_variant	3/7	1	NM_001206626.2	ENSP00000330216	P1
TRIM49B	ENST00000622138.4	c.475A>G	p.Asn159Asp	missense_variant	4/8	1		ENSP00000481457	P1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461270 Hom.: 0 Cov.: 34 AF XY: 0.00000413 AC XY: 3 AN XY: 726940

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000360

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 27, 2022

The c.475A>G (p.N159D) alteration is located in exon 2 (coding exon 2) of the TRIM49B gene. This alteration results from a A to G substitution at nucleotide position 475, causing the asparagine (N) at amino acid position 159 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.9
DANN	Benign	0.88
DEOGEN2	Benign	0.071	T;T
Eigen	Benign	-0.78
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.012	N
LIST_S2	Benign	0.54	.;T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.3	M;M
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.3	.;D
REVEL	Benign	0.063
Sift	Benign	0.056	.;T
Sift4G	Benign	0.087	T;T
Vest4		0.19
MutPred		0.58		Loss of MoRF binding (P = 0.0514);Loss of MoRF binding (P = 0.0514);
MVP		0.14
MPC		2.0
ClinPred		0.19	T
GERP RS		0.11
Varity_R		0.25
gMVP		0.022

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-49053891;