11-108339531-T-C

Variant names:

• chr11-108339531-T-C
• rs227069
• NM_000051.4:c.8268+3570T>C

Variant summary

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

The NM_000051.4(ATM):​c.8268+3570T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 151,760 control chromosomes in the GnomAD database, including 11,791 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 0.38 (11791 hom., cov: 31)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.71
• Publications: 9 publications found

Genes affected

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]

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000051.4. 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
	ATM	NM_000051.4	MANE Select	c.8268+3570T>C		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.8268+3570T>C		intron	N/A	NP_001338763.1
	C11orf65	NM_001330368.2		c.641-30460A>G		intron	N/A	NP_001317297.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000675843.1	MANE Select	c.8268+3570T>C		intron	N/A	ENSP00000501606.1
	ATM	ENST00000452508.7	TSL:1	c.8268+3570T>C		intron	N/A	ENSP00000388058.2
	C11orf65	ENST00000615746.4	TSL:1	c.*1197-4239A>G		intron	N/A	ENSP00000483537.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57232 AN: 151642 Hom.: 11783 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.314

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.567

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.655

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.423

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.377 AC: 57255 AN: 151760 Hom.: 11791 Cov.: 31 AF XY: 0.384 AC XY: 28502 AN XY: 74168

African (AFR) AF: 0.210 AC: 8673 AN: 41374

American (AMR) AF: 0.511 AC: 7795 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1719 AN: 3468

East Asian (EAS) AF: 0.415 AC: 2140 AN: 5160

South Asian (SAS) AF: 0.568 AC: 2723 AN: 4798

European-Finnish (FIN) AF: 0.390 AC: 4105 AN: 10518

Middle Eastern (MID) AF: 0.643 AC: 189 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28733 AN: 67888

Other (OTH) AF: 0.426 AC: 893 AN: 2096

Alfa AF: 0.410 Hom.: 8941

Bravo AF: 0.374

Asia WGS AF: 0.505 AC: 1754 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.18
DANN	Benign	0.50
PhyloP100		-3.7
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: rs227069; hg19: chr11-108210258;