chr1-155173998-C-G

Variant names:

• chr1-155173998-C-G
• rs199784137
• NM_025058.5:c.32C>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025058.5(TRIM46):​c.32C>G​(p.Thr11Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. 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. T11N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: TRIM46 NM_025058.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.52
• Publications: 0 publications found

Genes affected

TRIM46 (HGNC:19019): (tripartite motif containing 46) This gene encodes a protein of the tripartite motif (TRIM) family. The TRIM motif includes zinc-binding domains, a RING finger region, a B-box motif and a coiled-coil domain. TRIM46 is reported to be involved in the proliferation of multiple types of cancer cells including lung and breast cancer. It has also been shown to control neuronal polarity and axon specification by forming uniform microtubule bundles in the axon. [provided by RefSeq, May 2022]

ENSG00000273088 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17598826).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025058.5. 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
	TRIM46	NM_025058.5	MANE Select	c.32C>G	p.Thr11Ser	missense	Exon 1 of 10	NP_079334.3
	TRIM46	NM_001406245.1		c.32C>G	p.Thr11Ser	missense	Exon 1 of 11	NP_001393174.1
	TRIM46	NM_001406246.1		c.32C>G	p.Thr11Ser	missense	Exon 1 of 9	NP_001393175.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM46	ENST00000334634.9	TSL:1 MANE Select	c.32C>G	p.Thr11Ser	missense	Exon 1 of 10	ENSP00000334657.4	Q7Z4K8-1
	TRIM46	ENST00000368385.8	TSL:1	c.32C>G	p.Thr11Ser	missense	Exon 1 of 9	ENSP00000357369.4	Q7Z4K8-2
	ENSG00000273088	ENST00000473363.3	TSL:5	c.49-524G>C		intron	N/A	ENSP00000477381.3	V9GZ38

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0043	T
Eigen	Uncertain	0.22
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		4.5
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.14
Sift	Benign	0.57	T
Sift4G	Benign	0.61	T
Polyphen		1.0	D
Vest4		0.25
MutPred		0.24		Gain of disorder (P = 0.036)
MVP		0.51
MPC		0.79
ClinPred		0.54	D
GERP RS		5.0
PromoterAI		-0.019	Neutral
Varity_R		0.12
gMVP		0.82
Mutation Taster		=265/35	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs199784137; hg19: chr1-155146474;