17-54914650-C-T

Variant names:

• chr17-54914650-C-T
• rs756568791
• NM_005486.3:c.510C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_005486.3(TOM1L1):​c.510C>T​(p.Ile170Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000281 in 1,461,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000028 (0 hom.)
• Consequence: TOM1L1 NM_005486.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.574
• Publications: 2 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP7: Synonymous conserved (PhyloP=0.574 with no splicing effect.

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.510C>T	p.Ile170Ile	synonymous	Exon 6 of 16	NP_005477.2	O75674-1
	TOM1L1	NM_001321174.2		c.279C>T	p.Ile93Ile	synonymous	Exon 4 of 14	NP_001308103.1	O75674-3
	TOM1L1	NM_001321175.2		c.279C>T	p.Ile93Ile	synonymous	Exon 7 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.510C>T	p.Ile170Ile	synonymous	Exon 6 of 16	ENSP00000460823.1	O75674-1
	TOM1L1	ENST00000575333.5	TSL:1	c.510C>T	p.Ile170Ile	synonymous	Exon 6 of 10	ENSP00000458918.1	O75674-2
	TOM1L1	ENST00000576932.5	TSL:1	n.279C>T		non_coding_transcript_exon	Exon 4 of 11	ENSP00000461876.1	I3NI44

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000478 AC: 12 AN: 251292 AF XY: 0.0000663

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000281 AC: 41 AN: 1461014 Hom.: 0 Cov.: 30 AF XY: 0.0000427 AC XY: 31 AN XY: 726836

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39680

South Asian (SAS) AF: 0.000464 AC: 40 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53298

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111364

Other (OTH) AF: 0.0000166 AC: 1 AN: 60358

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	6.8
DANN	Benign	0.75
PhyloP100		0.57

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

dbSNP: rs756568791; hg19: chr17-52992011;