17-54912800-C-G

Variant names:

• chr17-54912800-C-G
• NM_005486.3:c.357C>G

Variant summary

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

The NM_005486.3(TOM1L1):​c.357C>G​(p.Ile119Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: TOM1L1 NM_005486.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.710
• Publications: 0 publications found

Genes affected

TOM1L1 (HGNC:11983): (target of myb1 like 1 membrane trafficking protein) Enables clathrin binding activity and protein kinase binding activity. Involved in negative regulation of mitotic nuclear division; positive regulation of protein phosphorylation; and signal transduction. Located in cytosol and endosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005486.3. 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
	TOM1L1	NM_005486.3	MANE Select	c.357C>G	p.Ile119Met	missense	Exon 4 of 16	NP_005477.2	O75674-1
	TOM1L1	NM_001321174.2		c.126C>G	p.Ile42Met	missense	Exon 2 of 14	NP_001308103.1	O75674-3
	TOM1L1	NM_001321175.2		c.126C>G	p.Ile42Met	missense	Exon 5 of 17	NP_001308104.1	O75674-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOM1L1	ENST00000575882.6	TSL:1 MANE Select	c.357C>G	p.Ile119Met	missense	Exon 4 of 16	ENSP00000460823.1	O75674-1
	TOM1L1	ENST00000575333.5	TSL:1	c.357C>G	p.Ile119Met	missense	Exon 4 of 10	ENSP00000458918.1	O75674-2
	TOM1L1	ENST00000576932.5	TSL:1	n.126C>G		non_coding_transcript_exon	Exon 2 of 11	ENSP00000461876.1	I3NI44

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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	0.31
BayesDel_addAF	Uncertain	0.026	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	0.16
Eigen_PC	Benign	0.11
FATHMM_MKL	Benign	0.72	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.0	M
PhyloP100		0.71
PrimateAI	Uncertain	0.68	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.28
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.99	D
Vest4		0.81
MutPred		0.77		Loss of stability (P = 0.0897)
MVP		0.67
MPC		0.57
ClinPred		0.91	D
GERP RS		1.4
Varity_R		0.75
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr17-52990161;