NM_001206626.2:c.41T>C

Variant names:

• chr11-49031640-T-C
• rs1422210538
• NM_001206626.2:c.41T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001206626.2(TRIM49B):​c.41T>C​(p.Ile14Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,664 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: TRIM49B NM_001206626.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.06
• Publications: 0 publications found

Genes affected

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

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=0.09145743).
• BP6: Variant 11-49031640-T-C is Benign according to our data. Variant chr11-49031640-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3182539.Status of the report is criteria_provided_single_submitter, 1 stars.

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.41T>C	p.Ile14Thr	missense	Exon 2 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.41T>C	p.Ile14Thr	missense	Exon 2 of 7	ENSP00000330216.7	A6NDI0
	TRIM49B	ENST00000622138.4	TSL:1	c.41T>C	p.Ile14Thr	missense	Exon 3 of 8	ENSP00000481457.1	A6NDI0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250562 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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000753 AC: 11 AN: 1461664 Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4 AN XY: 727140

African (AFR) AF: 0.0000896 AC: 3 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111842

Other (OTH) AF: 0.0000497 AC: 3 AN: 60378

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.076
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.058
DANN	Benign	0.073
DEOGEN2	Benign	0.0073	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00074	N
LIST_S2	Benign	0.11	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.091	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.61	N
PhyloP100		-3.1
PrimateAI	Benign	0.40	T
PROVEAN	Benign	2.5	N
REVEL	Benign	0.13
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Vest4		0.066
MutPred		0.49		Loss of stability (P = 0.0358)
MVP		0.095
MPC		0.0074
ClinPred		0.052	T
GERP RS		-0.98
Varity_R		0.017
gMVP		0.019
Mutation Taster		=99/1	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: rs1422210538; hg19: chr11-49053192; COSMIC: COSV60322233;