NM_025058.5:c.395C>G

Variant names:

• chr1-155175957-C-G
• rs1446005818
• NM_025058.5:c.395C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BS2

The NM_025058.5(TRIM46):​c.395C>G​(p.Ala132Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000343 in 1,456,940 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 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)
  • Exomes 𝑓: 0.0000034 (0 hom.)
• Consequence: TRIM46 NM_025058.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.783
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.395C>G	p.Ala132Gly	missense	Exon 3 of 10	NP_079334.3
	TRIM46	NM_001406245.1		c.482C>G	p.Ala161Gly	missense	Exon 4 of 11	NP_001393174.1
	TRIM46	NM_001256601.1		c.356C>G	p.Ala119Gly	missense	Exon 3 of 10	NP_001243530.1	Q7Z4K8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TRIM46	ENST00000334634.9	TSL:1 MANE Select	c.395C>G	p.Ala132Gly	missense	Exon 3 of 10	ENSP00000334657.4	Q7Z4K8-1
	TRIM46	ENST00000611379.1	TSL:1	c.356C>G	p.Ala119Gly	missense	Exon 3 of 10	ENSP00000478669.1	A0A087WUH1
	TRIM46	ENST00000368385.8	TSL:1	c.395C>G	p.Ala132Gly	missense	Exon 3 of 9	ENSP00000357369.4	Q7Z4K8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000343 AC: 5 AN: 1456940 Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2 AN XY: 724052

African (AFR) AF: 0.00 AC: 0 AN: 33414

American (AMR) AF: 0.00 AC: 0 AN: 44518

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25786

East Asian (EAS) AF: 0.00 AC: 0 AN: 39614

South Asian (SAS) AF: 0.00 AC: 0 AN: 85784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 0.00000361 AC: 4 AN: 1108610

Other (OTH) AF: 0.0000166 AC: 1 AN: 60200

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

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	0.10
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.77
DEOGEN2	Benign	0.0054	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.13
FATHMM_MKL	Benign	0.74	D
LIST_S2	Benign	0.79	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.20	N
PhyloP100		0.78
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	0.48	N
REVEL	Benign	0.086
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.40	B
Vest4		0.18
MutPred		0.42		Gain of disorder (P = 0.1717)
MVP		0.59
MPC		0.77
ClinPred		0.19	T
GERP RS		5.4
Varity_R		0.12
gMVP		0.17
Mutation Taster		=72/28	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: 0

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1446005818; hg19: chr1-155148433;