rs12949538

Positions:

• chr17-54933309-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005486.3(TOM1L1):​c.854+3103C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 152,190 control chromosomes in the GnomAD database, including 3,878 homozygotes. 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: 𝑓 0.21 (3878 hom., cov: 33)
• Consequence: TOM1L1 NM_005486.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.402

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.27 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOM1L1	NM_005486.3	c.854+3103C>T		intron_variant		ENST00000575882.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOM1L1	ENST00000575882.6	c.854+3103C>T		intron_variant		1	NM_005486.3	P1

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31716 AN: 152072 Hom.: 3879 Cov.: 33

Gnomad AFR AF: 0.0881

Gnomad AMI AF: 0.137

Gnomad AMR AF: 0.203

Gnomad ASJ AF: 0.240

Gnomad EAS AF: 0.129

Gnomad SAS AF: 0.165

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.227

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.208 AC: 31724 AN: 152190 Hom.: 3878 Cov.: 33 AF XY: 0.211 AC XY: 15699 AN XY: 74400

Gnomad4 AFR AF: 0.0881

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.240

Gnomad4 EAS AF: 0.129

Gnomad4 SAS AF: 0.166

Gnomad4 FIN AF: 0.321

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.228

Alfa AF: 0.246 Hom.: 1192

Bravo AF: 0.194

Asia WGS AF: 0.146 AC: 509 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs12949538; hg19: chr17-53010670;