rs673281

Variant names:

• chr11-108311342-G-A
• rs673281
• NM_000051.4:c.5918+1027G>A

Variant summary

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

The NM_000051.4(ATM):​c.5918+1027G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.62 in 151,948 control chromosomes in the GnomAD database, including 29,517 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. The gene ATM is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: 𝑓 0.62 (29517 hom., cov: 30)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800
• Publications: 10 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

Specifications for ATM are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.677 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.5918+1027G>A		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.5918+1027G>A		intron	N/A	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.641-2271C>T		intron	N/A	NP_001317297.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000675843.1	MANE Select	c.5918+1027G>A		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.5918+1027G>A		intron	N/A	ENSP00000388058.2	Q13315
	ATM	ENST00000527805.6	TSL:1	n.*982+1027G>A		intron	N/A	ENSP00000435747.2	E9PIN0

Frequencies

GnomAD3 genomes AF: 0.620 AC: 94120 AN: 151830 Hom.: 29487 Cov.: 30

Gnomad AFR AF: 0.684

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.662

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.577

Gnomad OTH AF: 0.630

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

GnomAD4 genome AF: 0.620 AC: 94196 AN: 151948 Hom.: 29517 Cov.: 30 AF XY: 0.624 AC XY: 46374 AN XY: 74272

African (AFR) AF: 0.684 AC: 28339 AN: 41446

American (AMR) AF: 0.662 AC: 10104 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2323 AN: 3464

East Asian (EAS) AF: 0.445 AC: 2297 AN: 5164

South Asian (SAS) AF: 0.654 AC: 3145 AN: 4812

European-Finnish (FIN) AF: 0.631 AC: 6659 AN: 10548

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

European-Non Finnish (NFE) AF: 0.577 AC: 39188 AN: 67936

Other (OTH) AF: 0.630 AC: 1329 AN: 2108

Alfa AF: 0.597 Hom.: 8745

Bravo AF: 0.622

Asia WGS AF: 0.601 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	3.0
DANN	Benign	0.74
PhyloP100		0.0080
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: rs673281; hg19: chr11-108182069;