11-108317539-ATTTT-ATTTTTT

Variant names:

• chr11-108317539-A-ATT
• rs58978479
• NM_000051.4:c.6347+30_6347+31dupTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_000051.4(ATM):​c.6347+30_6347+31dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.0 (0 hom., cov: 24)
  • Exomes 𝑓: 0.000044 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.405
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.6347+30_6347+31dupTT		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.6347+30_6347+31dupTT		intron	N/A	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.641-8470_641-8469dupAA		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.6347+18_6347+19insTT		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.6347+18_6347+19insTT		intron	N/A	ENSP00000388058.2	Q13315
	ATM	ENST00000527805.6	TSL:1	n.*1411+18_*1411+19insTT		intron	N/A	ENSP00000435747.2	E9PIN0

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 125156 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000491 AC: 5 AN: 101888 AF XY: 0.0000559

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000112

Gnomad NFE exome AF: 0.0000674

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000436 AC: 52 AN: 1192392 Hom.: 0 Cov.: 0 AF XY: 0.0000538 AC XY: 32 AN XY: 594974

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

African (AFR) AF: 0.00 AC: 0 AN: 28938

American (AMR) AF: 0.000106 AC: 4 AN: 37656

Ashkenazi Jewish (ASJ) AF: 0.000141 AC: 3 AN: 21346

East Asian (EAS) AF: 0.0000324 AC: 1 AN: 30874

South Asian (SAS) AF: 0.0000408 AC: 3 AN: 73528

European-Finnish (FIN) AF: 0.0000725 AC: 3 AN: 41376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4908

European-Non Finnish (NFE) AF: 0.0000387 AC: 35 AN: 904876

Other (OTH) AF: 0.0000614 AC: 3 AN: 48890

⚠️ 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 Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 125156 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 59948

African (AFR) AF: 0.00 AC: 0 AN: 34676

American (AMR) AF: 0.00 AC: 0 AN: 11920

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3070

East Asian (EAS) AF: 0.00 AC: 0 AN: 4258

South Asian (SAS) AF: 0.00 AC: 0 AN: 3950

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6474

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 256

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58100

Other (OTH) AF: 0.00 AC: 0 AN: 1672

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.41
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: rs58978479; hg19: chr11-108188266;