11-108326230-G-GT

Variant names:

• chr11-108326230-G-GT
• rs763287238
• NM_000051.4:c.6975+13dupT

Variant summary

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

The NM_000051.4(ATM):​c.6975+13dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000102 in 1,608,806 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000046 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.378
• 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 -8 ACMG points.

• BP6: Variant 11-108326230-G-GT is Benign according to our data. Variant chr11-108326230-G-GT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 220607.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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.6975+13dupT		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.6975+13dupT		intron	N/A	NP_001338763.1
	C11orf65	NM_001330368.2		c.641-17160dupA		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.6975+13dupT		intron	N/A	ENSP00000501606.1
	ATM	ENST00000452508.7	TSL:1	c.6975+13dupT		intron	N/A	ENSP00000388058.2
	ATM	ENST00000527805.6	TSL:1	n.*2039+13dupT		intron	N/A	ENSP00000435747.2

Frequencies

GnomAD3 genomes AF: 0.0000462 AC: 7 AN: 151592 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000589

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000926 AC: 23 AN: 248368 AF XY: 0.0000967

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000882

Gnomad ASJ exome AF: 0.000801

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000951

Gnomad NFE exome AF: 0.0000710

Gnomad OTH exome AF: 0.000165

GnomAD4 exome AF: 0.000108 AC: 157 AN: 1457214 Hom.: 0 Cov.: 32 AF XY: 0.000103 AC XY: 75 AN XY: 724958

African (AFR) AF: 0.0000899 AC: 3 AN: 33368

American (AMR) AF: 0.0000224 AC: 1 AN: 44552

Ashkenazi Jewish (ASJ) AF: 0.000961 AC: 25 AN: 26024

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39488

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86076

European-Finnish (FIN) AF: 0.000151 AC: 8 AN: 53106

Middle Eastern (MID) AF: 0.000869 AC: 5 AN: 5752

European-Non Finnish (NFE) AF: 0.0000929 AC: 103 AN: 1108634

Other (OTH) AF: 0.000149 AC: 9 AN: 60214

GnomAD4 genome AF: 0.0000462 AC: 7 AN: 151592 Hom.: 0 Cov.: 32 AF XY: 0.0000541 AC XY: 4 AN XY: 74002

African (AFR) AF: 0.0000484 AC: 2 AN: 41284

American (AMR) AF: 0.00 AC: 0 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.00 AC: 0 AN: 4790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10476

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000589 AC: 4 AN: 67858

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.000304 Hom.: 0

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Hereditary cancer-predisposing syndrome (3)
-	-	1	Ataxia-telangiectasia syndrome (1)
-	-	1	Ataxia-telangiectasia syndrome;C0346153:Familial cancer of breast (1)
-	-	1	Malignant tumor of breast (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs763287238; hg19: chr11-108196957; COSMIC: COSV53759063; COSMIC: COSV53759063;