chr11-108325985-CATT-C

Variant names:

• chr11-108325985-CATT-C
• rs3212322
• NM_000051.4:c.6808-60_6808-58delATT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_000051.4(ATM):​c.6808-60_6808-58delATT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.55 in 1,535,810 control chromosomes in the GnomAD database, including 237,239 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (20285 hom., cov: 0)
  • Exomes 𝑓: 0.56 (216954 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 3.05
• Publications: 1 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: Benign. The variant received -16 ACMG points.

• BP6: Variant 11-108325985-CATT-C is Benign according to our data. Variant chr11-108325985-CATT-C is described in ClinVar as Benign. ClinVar VariationId is 633055.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

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.6808-60_6808-58delATT		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.6808-60_6808-58delATT		intron	N/A	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.641-16917_641-16915delAAT		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.6808-72_6808-70delATT		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.6808-72_6808-70delATT		intron	N/A	ENSP00000388058.2	Q13315
	ATM	ENST00000527805.6	TSL:1	n.*1872-72_*1872-70delATT		intron	N/A	ENSP00000435747.2	E9PIN0

Frequencies

GnomAD3 genomes AF: 0.501 AC: 75883 AN: 151486 Hom.: 20272 Cov.: 0

Gnomad AFR AF: 0.300

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.608

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.731

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.544

GnomAD4 exome AF: 0.556 AC: 769167 AN: 1384206 Hom.: 216954 AF XY: 0.559 AC XY: 386533 AN XY: 691182

African (AFR) AF: 0.293 AC: 9318 AN: 31842

American (AMR) AF: 0.629 AC: 26873 AN: 42714

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 15583 AN: 25452

East Asian (EAS) AF: 0.415 AC: 16153 AN: 38952

South Asian (SAS) AF: 0.598 AC: 49650 AN: 83066

European-Finnish (FIN) AF: 0.626 AC: 31549 AN: 50426

Middle Eastern (MID) AF: 0.713 AC: 3741 AN: 5244

European-Non Finnish (NFE) AF: 0.557 AC: 584530 AN: 1048768

Other (OTH) AF: 0.550 AC: 31770 AN: 57742

GnomAD4 genome AF: 0.501 AC: 75916 AN: 151604 Hom.: 20285 Cov.: 0 AF XY: 0.509 AC XY: 37683 AN XY: 74028

African (AFR) AF: 0.300 AC: 12418 AN: 41354

American (AMR) AF: 0.608 AC: 9252 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2221 AN: 3468

East Asian (EAS) AF: 0.414 AC: 2136 AN: 5158

South Asian (SAS) AF: 0.603 AC: 2900 AN: 4808

European-Finnish (FIN) AF: 0.629 AC: 6587 AN: 10480

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38461 AN: 67818

Other (OTH) AF: 0.545 AC: 1146 AN: 2104

Alfa AF: 0.527 Hom.: 2658

Bravo AF: 0.489

Asia WGS AF: 0.533 AC: 1852 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	1	Ataxia-telangiectasia syndrome (1)
-	-	1	Hereditary breast ovarian cancer syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.0
Mutation Taster		=100/0	polymorphism (auto)

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: rs3212322; hg19: chr11-108196712; COSMIC: COSV107218861; COSMIC: COSV107218861;