11-108317539-ATTTT-ATT

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000051.4(ATM):​c.6347+30_6347+31delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00115 in 1,298,164 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000080 (0 hom., cov: 23)
  • Exomes 𝑓: 0.0013 (0 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.405
• 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: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 11-108317539-ATT-A is Benign according to our data. Variant chr11-108317539-ATT-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2442804.Status of the report is criteria_provided_single_submitter, 1 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.6347+30_6347+31delTT		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.6347+30_6347+31delTT		intron	N/A	NP_001338763.1
	C11orf65	NM_001330368.2		c.641-8470_641-8469delAA		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+20delTT		intron	N/A	ENSP00000501606.1
	ATM	ENST00000452508.7	TSL:1	c.6347+19_6347+20delTT		intron	N/A	ENSP00000388058.2
	ATM	ENST00000527805.6	TSL:1	n.*1411+19_*1411+20delTT		intron	N/A	ENSP00000435747.2

Frequencies

GnomAD3 genomes AF: 0.00000799 AC: 1 AN: 125140 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: 0.000155

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00291 AC: 296 AN: 101888 AF XY: 0.00268

Gnomad AFR exome AF: 0.0134

Gnomad AMR exome AF: 0.00255

Gnomad ASJ exome AF: 0.00200

Gnomad EAS exome AF: 0.00278

Gnomad FIN exome AF: 0.000224

Gnomad NFE exome AF: 0.00130

Gnomad OTH exome AF: 0.00243

GnomAD4 exome AF: 0.00127 AC: 1494 AN: 1173024 Hom.: 0 AF XY: 0.00128 AC XY: 748 AN XY: 585382

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

African (AFR) AF: 0.0135 AC: 378 AN: 27908

American (AMR) AF: 0.00193 AC: 71 AN: 36826

Ashkenazi Jewish (ASJ) AF: 0.00205 AC: 43 AN: 20936

East Asian (EAS) AF: 0.00300 AC: 90 AN: 30020

South Asian (SAS) AF: 0.000887 AC: 64 AN: 72148

European-Finnish (FIN) AF: 0.00165 AC: 67 AN: 40616

Middle Eastern (MID) AF: 0.00124 AC: 6 AN: 4842

European-Non Finnish (NFE) AF: 0.000738 AC: 658 AN: 891698

Other (OTH) AF: 0.00244 AC: 117 AN: 48030

⚠️ 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: 125140 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 59940

⚠️ 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: 3068

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 3948

European-Finnish (FIN) AF: 0.000155 AC: 1 AN: 6472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 254

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 58092

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.

Alfa AF: 0.00387 Hom.: 6

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Breast and/or ovarian cancer (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism

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;