chr11-108354934-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000615746(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 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.696

Variant links:

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]

C11orf65 links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 1169174.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr11-108354934-A-G is described in Lovd as [Benign].

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 link	c.8850+60A>G		intron_variant	Intron 61 of 62	ENST00000675843.1	NP_000042.3	Q13315A0A024R3C7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1 link	c.8850+60A>G		intron_variant	Intron 61 of 62		NM_000051.4	ENSP00000501606.1		Q13315

Frequencies

GnomAD3 genomes

AF:

0.618

AC:

93911

AN:

151958

Hom.:

29289

Cov.:

show subpopulations

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.:

AF XY:

0.587

AC XY:

367518

AN XY:

626590

show subpopulations

Gnomad4 AFR exome

AF:

0.678

Gnomad4 AMR exome

AF:

0.658

Gnomad4 ASJ exome

AF:

0.645

Gnomad4 EAS exome

AF:

0.466

Gnomad4 SAS exome

AF:

0.648

Gnomad4 FIN exome

AF:

0.626

Gnomad4 NFE exome

AF:

0.570

Gnomad4 OTH exome

AF:

0.595

GnomAD4 genome

AF:

0.618

AC:

93986

AN:

152078

Hom.:

29318

Cov.:

AF XY:

0.622

AC XY:

46256

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.676

Gnomad4 AMR

AF:

0.661

Gnomad4 ASJ

AF:

0.670

Gnomad4 EAS

AF:

0.445

Gnomad4 SAS

AF:

0.652

Gnomad4 FIN

AF:

0.631

Gnomad4 NFE

AF:

0.577

Gnomad4 OTH

AF:

0.628

Alfa

AF:

0.604

Hom.:

28184

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

LINK: link

Submissions by phenotype

not specified

Benign:3

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

- -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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) -

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

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over