17-54938956-A-C

Variant names:

• chr17-54938956-A-C
• NM_005486.3:c.1066A>C

Variant summary

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

The NM_005486.3(TOM1L1):​c.1066A>C​(p.Asn356His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 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)
• Consequence: TOM1L1 NM_005486.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.950
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07119295).

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.1066A>C	p.Asn356His	missense	Exon 11 of 16	NP_005477.2	O75674-1
	TOM1L1	NM_001321174.2		c.835A>C	p.Asn279His	missense	Exon 9 of 14	NP_001308103.1	O75674-3
	TOM1L1	NM_001321175.2		c.835A>C	p.Asn279His	missense	Exon 12 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.1066A>C	p.Asn356His	missense	Exon 11 of 16	ENSP00000460823.1	O75674-1
	TOM1L1	ENST00000576932.5	TSL:1	n.835A>C		non_coding_transcript_exon	Exon 9 of 11	ENSP00000461876.1	I3NI44
	TOM1L1	ENST00000851795.1		c.1066A>C	p.Asn356His	missense	Exon 11 of 17	ENSP00000521854.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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	0.066
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.071	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L
PhyloP100		0.95
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.053
Sift	Benign	0.15	T
Sift4G	Benign	0.41	T
Polyphen		0.0010	B
Vest4		0.16
MutPred		0.26		Loss of solvent accessibility (P = 0.1744)
MVP		0.28
MPC		0.12
ClinPred		0.14	T
GERP RS		2.9
PromoterAI		0.015	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.053
gMVP		0.39

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

hg19: chr17-53016317;