1-155175558-C-G

Variant names:

• chr1-155175558-C-G
• NM_025058.5:c.236C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_025058.5(TRIM46):​c.236C>G​(p.Ser79Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,454,708 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: TRIM46 NM_025058.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.17
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3190763).

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.236C>G	p.Ser79Cys	missense	Exon 2 of 10	NP_079334.3
	TRIM46	NM_001406245.1		c.323C>G	p.Ser108Cys	missense	Exon 3 of 11	NP_001393174.1
	TRIM46	NM_001256601.1		c.197C>G	p.Ser66Cys	missense	Exon 2 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.236C>G	p.Ser79Cys	missense	Exon 2 of 10	ENSP00000334657.4	Q7Z4K8-1
	TRIM46	ENST00000611379.1	TSL:1	c.197C>G	p.Ser66Cys	missense	Exon 2 of 10	ENSP00000478669.1	A0A087WUH1
	TRIM46	ENST00000368385.8	TSL:1	c.236C>G	p.Ser79Cys	missense	Exon 2 of 9	ENSP00000357369.4	Q7Z4K8-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1454708 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 723578

African (AFR) AF: 0.00 AC: 0 AN: 33256

American (AMR) AF: 0.00 AC: 0 AN: 43640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25812

East Asian (EAS) AF: 0.00 AC: 0 AN: 38824

South Asian (SAS) AF: 0.00 AC: 0 AN: 85188

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53228

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1108910

Other (OTH) AF: 0.00 AC: 0 AN: 60102

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	Uncertain	0.49
BayesDel_addAF	Benign	-0.0021	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.027	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		7.2
PrimateAI	Uncertain	0.64	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.12
Sift	Benign	0.13	T
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.49
MutPred		0.23		Loss of glycosylation at S79 (P = 0.0044)
MVP		0.48
MPC		1.8
ClinPred		0.99	D
GERP RS		4.5
Varity_R		0.25
gMVP		0.49
Mutation Taster		=58/42	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

hg19: chr1-155148034; COSMIC: COSV55278720; COSMIC: COSV55278720;