11-72108241-G-A

Position:

• chr11-72108241-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001393500.2(TOMT):​c.456+122G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 875,062 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0080 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00090 (10 hom.)
• Consequence: TOMT NM_001393500.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.858

Genes affected

TOMT (HGNC:55527): (transmembrane O-methyltransferase) This gene encodes a catechol-O-methyltransferase that catalyzes the transfer of a methyl group from S-adenosyl-L-methionine to a hydroxyl group of catechols and is essential for auditory and vestibular function. Mutations in this gene have been associated with nonsyndromic deafness. Readthrough transcription is observed across this gene and the adjacent leucine-rich repeat containing 51 gene. A third locus (GeneID:220074) is defined to represent the readthrough transcripts. [provided by RefSeq, Feb 2021]

LRTOMT (HGNC:):

ANAPC15 (HGNC:24531): (anaphase promoting complex subunit 15) Involved in regulation of mitotic cell cycle spindle assembly checkpoint. Part of anaphase-promoting complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 11-72108241-G-A is Benign according to our data. Variant chr11-72108241-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1196151.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00803 (1222/152258) while in subpopulation AFR AF= 0.0279 (1159/41536). AF 95% confidence interval is 0.0266. There are 11 homozygotes in gnomad4. There are 556 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TOMT	NM_001393500.2	c.456+122G>A		intron_variant		ENST00000541899.3
LRTOMT	NM_001145309.4	c.555+122G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TOMT	ENST00000541899.3	c.456+122G>A		intron_variant		5	NM_001393500.2	P1
ANAPC15	ENST00000502597.2	c.64-636C>T		intron_variant		1
ANAPC15	ENST00000543050.5	c.319-636C>T		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00803 AC: 1222 AN: 152140 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0280

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00281

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00335

GnomAD4 exome AF: 0.000905 AC: 654 AN: 722804 Hom.: 10 AF XY: 0.000849 AC XY: 306 AN XY: 360412

Gnomad4 AFR exome AF: 0.0291

Gnomad4 AMR exome AF: 0.00200

Gnomad4 ASJ exome AF: 0.000204

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000257

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000599

Gnomad4 OTH exome AF: 0.00206

GnomAD4 genome AF: 0.00803 AC: 1222 AN: 152258 Hom.: 11 Cov.: 32 AF XY: 0.00747 AC XY: 556 AN XY: 74462

Gnomad4 AFR AF: 0.0279

Gnomad4 AMR AF: 0.00281

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00332

Alfa AF: 0.00659 Hom.: 1

Bravo AF: 0.00953

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 31, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	15
DANN	Benign	0.78

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: rs114709976; hg19: chr11-71819287;