11-108355298-A-G

Variant names:

• chr11-108355298-A-G
• rs652541
• ENST00000615746.4:c.*813T>C

Variant summary

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

The ENST00000615746.4(C11orf65):​c.*813T>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 0.604 in 215,928 control chromosomes in the GnomAD database, including 40,146 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 0.62 (29385 hom., cov: 32)
  • Exomes 𝑓: 0.57 (10761 hom.)
• Consequence: C11orf65 ENST00000615746.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.99
• Publications: 10 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):

• ATM-related cancer predisposition

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• hereditary breast carcinoma

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

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

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

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• gastric carcinoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.672 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000615746.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.8850+424A>G		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.8850+424A>G		intron	N/A	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.640+30622T>C		intron	N/A	NP_001317297.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C11orf65	ENST00000615746.4	TSL:1	c.*813T>C		3_prime_UTR	Exon 11 of 13	ENSP00000483537.1	Q8NCR3-1
	ATM	ENST00000675843.1	MANE Select	c.8850+424A>G		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.8850+424A>G		intron	N/A	ENSP00000388058.2	Q13315

Frequencies

GnomAD3 genomes AF: 0.619 AC: 93981 AN: 151900 Hom.: 29357 Cov.: 32

Gnomad AFR AF: 0.679

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.446

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.631

GnomAD4 exome AF: 0.569 AC: 36396 AN: 63910 Hom.: 10761 Cov.: 0 AF XY: 0.577 AC XY: 19591 AN XY: 33946

African (AFR) AF: 0.661 AC: 893 AN: 1352

American (AMR) AF: 0.660 AC: 2485 AN: 3766

Ashkenazi Jewish (ASJ) AF: 0.625 AC: 837 AN: 1340

East Asian (EAS) AF: 0.441 AC: 1501 AN: 3400

South Asian (SAS) AF: 0.644 AC: 5984 AN: 9294

European-Finnish (FIN) AF: 0.589 AC: 1502 AN: 2548

Middle Eastern (MID) AF: 0.740 AC: 145 AN: 196

European-Non Finnish (NFE) AF: 0.547 AC: 21190 AN: 38738

Other (OTH) AF: 0.567 AC: 1859 AN: 3276

GnomAD4 genome AF: 0.619 AC: 94054 AN: 152018 Hom.: 29385 Cov.: 32 AF XY: 0.623 AC XY: 46295 AN XY: 74294

African (AFR) AF: 0.679 AC: 28119 AN: 41428

American (AMR) AF: 0.661 AC: 10108 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2325 AN: 3470

East Asian (EAS) AF: 0.446 AC: 2307 AN: 5170

South Asian (SAS) AF: 0.653 AC: 3152 AN: 4826

European-Finnish (FIN) AF: 0.630 AC: 6647 AN: 10550

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

European-Non Finnish (NFE) AF: 0.577 AC: 39252 AN: 67972

Other (OTH) AF: 0.631 AC: 1332 AN: 2112

Alfa AF: 0.611 Hom.: 5449

Bravo AF: 0.620

Asia WGS AF: 0.600 AC: 2085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.11
DANN	Benign	0.60
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs652541; hg19: chr11-108226025;