rs1555091084

Variant names:

• chr11-108280980-T-TTA
• rs1555091084
• NM_000051.4:c.3403-15_3403-14insTA

Your query was ambiguous. Multiple possible variants found:

• chr11-108280980-T-TTA
• chr11-108280980-T-TTTA

Variant summary

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

The NM_000051.4(ATM):​c.3403-15_3403-14insTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000535 in 1,556,992 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00057 (1 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.133
• 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]

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 -8 ACMG points.

• BP6: Variant 11-108280980-T-TTA is Benign according to our data. Variant chr11-108280980-T-TTA is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 490530.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.3403-15_3403-14insTA		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.3403-15_3403-14insTA		intron	N/A	NP_001338763.1	Q13315

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000675843.1	MANE Select	c.3403-15_3403-14insTA		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.3403-15_3403-14insTA		intron	N/A	ENSP00000388058.2	Q13315
	ATM	ENST00000531525.3	TSL:1	c.3403-15_3403-14insTA		intron	N/A	ENSP00000434327.3	H0YDU7

Frequencies

GnomAD3 genomes AF: 0.000211 AC: 32 AN: 151728 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000857

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000556 AC: 129 AN: 231976 AF XY: 0.000548

Gnomad AFR exome AF: 0.000200

Gnomad AMR exome AF: 0.000673

Gnomad ASJ exome AF: 0.00131

Gnomad EAS exome AF: 0.000114

Gnomad FIN exome AF: 0.00114

Gnomad NFE exome AF: 0.000468

Gnomad OTH exome AF: 0.000898

GnomAD4 exome AF: 0.000570 AC: 801 AN: 1405146 Hom.: 1 Cov.: 31 AF XY: 0.000564 AC XY: 395 AN XY: 700236

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000443 AC: 14 AN: 31630

American (AMR) AF: 0.000673 AC: 28 AN: 41610

Ashkenazi Jewish (ASJ) AF: 0.00195 AC: 49 AN: 25076

East Asian (EAS) AF: 0.000178 AC: 7 AN: 39220

South Asian (SAS) AF: 0.000382 AC: 31 AN: 81180

European-Finnish (FIN) AF: 0.000852 AC: 44 AN: 51630

Middle Eastern (MID) AF: 0.00109 AC: 6 AN: 5524

European-Non Finnish (NFE) AF: 0.000550 AC: 589 AN: 1071106

Other (OTH) AF: 0.000567 AC: 33 AN: 58170

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000211 AC: 32 AN: 151846 Hom.: 0 Cov.: 0 AF XY: 0.000242 AC XY: 18 AN XY: 74258

African (AFR) AF: 0.000217 AC: 9 AN: 41402

American (AMR) AF: 0.00 AC: 0 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.000857 AC: 9 AN: 10500

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67902

Other (OTH) AF: 0.000475 AC: 1 AN: 2106

Alfa AF: 0.00265 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary cancer-predisposing syndrome (2)
-	-	1	ATM-related disorder (1)
-	-	1	Breast and/or ovarian cancer (1)
-	-	1	Familial ovarian cancer (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs1555091084; hg19: chr11-108151707;