11-108354934-A-G

Variant names:

• chr11-108354934-A-G
• rs664143
• ENST00000615746.4:c.*1177T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000615746.4(C11orf65):​c.*1177T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 1,389,134 control chromosomes in the GnomAD database, including 241,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.62 (29318 hom., cov: 32)
  • Exomes 𝑓: 0.58 (212111 hom.)
• Consequence: C11orf65 ENST00000615746.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.696
• Publications: 76 publications found

Genes affected

C11orf65 (HGNC:28519): (chromosome 11 open reading frame 65) Predicted to be involved in negative regulation of mitochondrial fission and negative regulation of protein targeting to mitochondrion. Predicted to be located in cytosol and mitochondrial outer membrane. [provided by Alliance of Genome Resources, Apr 2022]

ATM (HGNC:795): (ATM serine/threonine kinase) The protein encoded by this gene belongs to the PI3/PI4-kinase family. This protein is an important cell cycle checkpoint kinase that phosphorylates; thus, it functions as a regulator of a wide variety of downstream proteins, including tumor suppressor proteins p53 and BRCA1, checkpoint kinase CHK2, checkpoint proteins RAD17 and RAD9, and DNA repair protein NBS1. This protein and the closely related kinase ATR are thought to be master controllers of cell cycle checkpoint signaling pathways that are required for cell response to DNA damage and for genome stability. Mutations in this gene are associated with ataxia telangiectasia, an autosomal recessive disorder. [provided by RefSeq, Aug 2010]

ATM Gene-Disease associations (from GenCC):

• hereditary breast carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
• ataxia telangiectasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Laboratory for Molecular Medicine, Orphanet
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
• prostate cancer

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• sarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• familial ovarian cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• gastric carcinoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 11-108354934-A-G is Benign according to our data. Variant chr11-108354934-A-G is described in ClinVar as Benign. ClinVar VariationId is 1169174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.67 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4	c.8850+60A>G		intron_variant	Intron 61 of 62	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.8850+60A>G		intron_variant	Intron 61 of 62		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93911 AN: 151958 Hom.: 29289 Cov.: 32

Gnomad AFR AF: 0.676

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.628

GnomAD4 exome AF: 0.583 AC: 721636 AN: 1237056 Hom.: 212111 Cov.: 18 AF XY: 0.587 AC XY: 367518 AN XY: 626590

African (AFR) AF: 0.678 AC: 19629 AN: 28954

American (AMR) AF: 0.658 AC: 29080 AN: 44170

Ashkenazi Jewish (ASJ) AF: 0.645 AC: 15965 AN: 24754

East Asian (EAS) AF: 0.466 AC: 17977 AN: 38588

South Asian (SAS) AF: 0.648 AC: 52901 AN: 81588

European-Finnish (FIN) AF: 0.626 AC: 31035 AN: 49552

Middle Eastern (MID) AF: 0.752 AC: 4044 AN: 5380

European-Non Finnish (NFE) AF: 0.570 AC: 519428 AN: 911030

Other (OTH) AF: 0.595 AC: 31577 AN: 53040

GnomAD4 genome AF: 0.618 AC: 93986 AN: 152078 Hom.: 29318 Cov.: 32 AF XY: 0.622 AC XY: 46256 AN XY: 74310

African (AFR) AF: 0.676 AC: 28062 AN: 41484

American (AMR) AF: 0.661 AC: 10096 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2324 AN: 3470

East Asian (EAS) AF: 0.445 AC: 2306 AN: 5178

South Asian (SAS) AF: 0.652 AC: 3145 AN: 4820

European-Finnish (FIN) AF: 0.631 AC: 6669 AN: 10566

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.577 AC: 39249 AN: 67980

Other (OTH) AF: 0.628 AC: 1327 AN: 2112

Alfa AF: 0.593 Hom.: 68623

Bravo AF: 0.620

Asia WGS AF: 0.599 AC: 2084 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 12, 2023

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 70% of patients studied by a panel of primary immunodeficiencies. Number of patients: 67. Only high quality variants are reported. -

-

Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 16497724) -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Ataxia-telangiectasia syndrome Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hereditary breast ovarian cancer syndrome Benign:1

Apr 19, 2022

National Health Laboratory Service, Universitas Academic Hospital and University of the Free State

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.53
DANN	Benign	0.37
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs664143; hg19: chr11-108225661; COSMIC: COSV53746535;