NM_000051.4:c.6347+28_6347+31delTTTT

Variant names:

• chr11-108317539-ATTTT-A
• rs58978479
• NM_000051.4:c.6347+28_6347+31delTTTT

Variant summary

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

The NM_000051.4(ATM):​c.6347+28_6347+31delTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000531 in 1,318,348 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000080 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0000050 (0 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.568
• Publications: 4 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: 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.6347+28_6347+31delTTTT		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.6347+28_6347+31delTTTT		intron	N/A	NP_001338763.1
	C11orf65	NM_001330368.2		c.641-8472_641-8469delAAAA		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.6347+19_6347+22delTTTT		intron	N/A	ENSP00000501606.1
	ATM	ENST00000452508.7	TSL:1	c.6347+19_6347+22delTTTT		intron	N/A	ENSP00000388058.2
	ATM	ENST00000527805.6	TSL:1	n.*1411+19_*1411+22delTTTT		intron	N/A	ENSP00000435747.2

Frequencies

GnomAD3 genomes AF: 0.00000799 AC: 1 AN: 125156 Hom.: 0 Cov.: 23

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: 0.000154

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 101888 AF XY: 0.00

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: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000503 AC: 6 AN: 1193192 Hom.: 0 AF XY: 0.00000672 AC XY: 4 AN XY: 595328

⚠️ 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: 28944

American (AMR) AF: 0.00 AC: 0 AN: 37684

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21364

East Asian (EAS) AF: 0.0000324 AC: 1 AN: 30900

South Asian (SAS) AF: 0.00 AC: 0 AN: 73546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41428

Middle Eastern (MID) AF: 0.000204 AC: 1 AN: 4910

European-Non Finnish (NFE) AF: 0.00000442 AC: 4 AN: 905488

Other (OTH) AF: 0.00 AC: 0 AN: 48928

⚠️ 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: 0.00000799 AC: 1 AN: 125156 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 59948

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

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: 0.000154 AC: 1 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

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.57

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: rs58978479; hg19: chr11-108188266;