ENST00000781607.1:n.67+818A>G

Variant names:

• chr17-17843427-A-G
• rs6502618
• ENST00000781607.1:n.67+818A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000781607.1(ENSG00000301763):​n.67+818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.539 in 152,146 control chromosomes in the GnomAD database, including 23,278 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 0.54 (23278 hom., cov: 34)
  • Exomes 𝑓: 0.70 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: ENSG00000301763 ENST00000781607.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 6 publications found

Genes affected

ENSG00000301763 (HGNC:):

TOM1L2 (HGNC:11984): (target of myb1 like 2 membrane trafficking protein) This gene belongs to a small gene family whose members have an N-terminal VHS domain followed by a GAT domain; domains which typically participate in vesicular trafficking. The canonical protein encoded by this gene also has a C-terminal clathrin binding motif. This protein has been shown to interact with Tollip, clathrin and ubiquitin and is thought to play a role in endosomal sorting. This gene resides in the 3.7 Mb deletion of chromosome region 17p11.2 that is associated with Smith-Magenis syndrome. Alternative splicing results in multiple transcript variants encoding distinct proteins. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000781607.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	TOM1L2	NM_001082968.2	MANE Select	c.*4208T>C		downstream_gene	N/A	NP_001076437.1
	TOM1L2	NM_001350332.2		c.*4208T>C		downstream_gene	N/A	NP_001337261.1
	TOM1L2	NM_001350333.2		c.*4208T>C		downstream_gene	N/A	NP_001337262.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000301763	ENST00000781607.1		n.67+818A>G		intron	N/A
	TOM1L2	ENST00000379504.8	TSL:2 MANE Select	c.*4208T>C		downstream_gene	N/A	ENSP00000368818.3
	TOM1L2	ENST00000581396.6	TSL:1	c.*4208T>C		downstream_gene	N/A	ENSP00000464297.1

Frequencies

GnomAD3 genomes AF: 0.539 AC: 81988 AN: 152026 Hom.: 23263 Cov.: 34

Gnomad AFR AF: 0.500

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.0652

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.562

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.631

Gnomad OTH AF: 0.536

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.700 AC: 7 AN: 10 Hom.: 2 AF XY: 0.667 AC XY: 4 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.750 AC: 3 AN: 4

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.667 AC: 4 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.539 AC: 82052 AN: 152146 Hom.: 23278 Cov.: 34 AF XY: 0.527 AC XY: 39176 AN XY: 74362

African (AFR) AF: 0.500 AC: 20740 AN: 41498

American (AMR) AF: 0.464 AC: 7091 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1918 AN: 3472

East Asian (EAS) AF: 0.0652 AC: 338 AN: 5184

South Asian (SAS) AF: 0.273 AC: 1315 AN: 4824

European-Finnish (FIN) AF: 0.562 AC: 5952 AN: 10592

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.631 AC: 42895 AN: 67964

Other (OTH) AF: 0.536 AC: 1134 AN: 2114

Alfa AF: 0.574 Hom.: 3163

Bravo AF: 0.531

Asia WGS AF: 0.247 AC: 864 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.082
DANN	Benign	0.58
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6502618; hg19: chr17-17746741;