11-49034324-T-C

Position:

• chr11-49034324-T-C

Variant summary

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

The NM_001206626.2(TRIM49B):​c.686T>C​(p.Met229Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM49B NM_001206626.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.97

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=0.13854578).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TRIM49B	NM_001206626.2	c.686T>C	p.Met229Thr	missense_variant	4/7	ENST00000332682.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TRIM49B	ENST00000332682.9	c.686T>C	p.Met229Thr	missense_variant	4/7	1	NM_001206626.2	P1
TRIM49B	ENST00000622138.4	c.686T>C	p.Met229Thr	missense_variant	5/8	1		P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 35

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Oct 05, 2022

The c.686T>C (p.M229T) alteration is located in exon 3 (coding exon 3) of the TRIM49B gene. This alteration results from a T to C substitution at nucleotide position 686, causing the methionine (M) at amino acid position 229 to be replaced by a threonine (T). 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	0.23
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.22
DANN	Benign	0.23
DEOGEN2	Benign	0.081	T;T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0012	N
M_CAP	Benign	0.0013	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.6	L;L
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.63	T
Sift4G	Benign	0.15	T;T
Vest4		0.13
MutPred		0.60		Loss of stability (P = 0.0322);Loss of stability (P = 0.0322);
MVP		0.072
MPC		2.0
ClinPred		0.20	T
GERP RS		-1.2
Varity_R		0.10
gMVP		0.19

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

LitVar

Other links and lift over

dbSNP: rs1854492404; hg19: chr11-49055876;