chr17-54938956-A-C

Position:

• chr17-54938956-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 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. 15/21 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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOM1L1	NM_005486.3	c.1066A>C	p.Asn356His	missense_variant	11/16	ENST00000575882.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOM1L1	ENST00000575882.6	c.1066A>C	p.Asn356His	missense_variant	11/16	1	NM_005486.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 29, 2023

The c.1066A>C (p.N356H) alteration is located in exon 11 (coding exon 11) of the TOM1L1 gene. This alteration results from a A to C substitution at nucleotide position 1066, causing the asparagine (N) at amino acid position 356 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;.;.;T;.
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.30
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.56	T;T;.;T;T
M_CAP	Benign	0.0040	T
MetaRNN	Benign	0.071	T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L;.;.;.;.
MutationTaster	Benign	0.64	N;N;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.2	.;N;N;.;N
REVEL	Benign	0.053
Sift	Benign	0.15	.;T;T;.;T
Sift4G	Benign	0.41	T;T;T;T;T
Polyphen		0.0010	B;.;.;.;.
Vest4		0.16
MutPred		0.26		Loss of solvent accessibility (P = 0.1744);Loss of solvent accessibility (P = 0.1744);.;.;.;
MVP		0.28
MPC		0.12
ClinPred		0.14	T
GERP RS		2.9
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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-53016317;