rs587781324

Variant names:

• chr11-108332905-GT-G
• rs587781324
• NM_000051.4:c.7927+13delT

Your query was ambiguous. Multiple possible variants found:

• chr11-108332905-GT-G
• chr11-108332905-GT-GTT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP6_Very_Strong

The NM_000051.4(ATM):​c.7927+13delT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000807 in 1,610,286 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★). The gene ATM is included in the ClinGen Criteria Specification Registry.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000069 (0 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.00
• Publications: 0 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 -8 ACMG points.

• BP6: Variant 11-108332905-GT-G is Benign according to our data. Variant chr11-108332905-GT-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 422794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.7927+13delT		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.7927+13delT		intron	N/A	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.641-23835delA		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.7927+13delT		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.7927+13delT		intron	N/A	ENSP00000388058.2	Q13315
	C11orf65	ENST00000615746.4	TSL:1	c.*1270-1339delA		intron	N/A	ENSP00000483537.1	Q8NCR3-1

Frequencies

GnomAD3 genomes AF: 0.0000198 AC: 3 AN: 151892 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 248182 AF XY: 0.0000223

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000886

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000686 AC: 10 AN: 1458394 Hom.: 0 Cov.: 31 AF XY: 0.00000965 AC XY: 7 AN XY: 725670

African (AFR) AF: 0.000120 AC: 4 AN: 33434

American (AMR) AF: 0.00 AC: 0 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39572

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51390

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110954

Other (OTH) AF: 0.00 AC: 0 AN: 60318

GnomAD4 genome AF: 0.0000198 AC: 3 AN: 151892 Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2 AN XY: 74164

African (AFR) AF: 0.00 AC: 0 AN: 41342

American (AMR) AF: 0.000131 AC: 2 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Ataxia-telangiectasia syndrome (1)
-	-	1	Ataxia-telangiectasia syndrome;C0346153:Familial cancer of breast (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.0
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs587781324;

hg19: chr11-108203632;

COSMIC: COSV53728615;

COSMIC: COSV53728615;