11-108325554-A-G

Variant names:

• chr11-108325554-A-G
• rs924117395
• NM_000051.4:c.6807+10A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_000051.4(ATM):​c.6807+10A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000572 in 1,574,588 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000049 (0 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.29
• 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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-108325554-A-G is Benign according to our data. Variant chr11-108325554-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 414615.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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.6807+10A>G		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.6807+10A>G		intron	N/A	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.641-16483T>C		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.6807+10A>G		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.6807+10A>G		intron	N/A	ENSP00000388058.2	Q13315
	ATM	ENST00000527805.6	TSL:1	n.*1871+10A>G		intron	N/A	ENSP00000435747.2	E9PIN0

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152160 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

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

GnomAD4 exome AF: 0.00000492 AC: 7 AN: 1422310 Hom.: 0 Cov.: 29 AF XY: 0.00000282 AC XY: 2 AN XY: 709870

African (AFR) AF: 0.00 AC: 0 AN: 32692

American (AMR) AF: 0.00 AC: 0 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25920

East Asian (EAS) AF: 0.00 AC: 0 AN: 39480

South Asian (SAS) AF: 0.00 AC: 0 AN: 85470

European-Finnish (FIN) AF: 0.0000206 AC: 1 AN: 48636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5712

European-Non Finnish (NFE) AF: 0.00000278 AC: 3 AN: 1080532

Other (OTH) AF: 0.0000507 AC: 3 AN: 59204

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152278 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74470

African (AFR) AF: 0.00 AC: 0 AN: 41560

American (AMR) AF: 0.0000653 AC: 1 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2112

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Ataxia-telangiectasia syndrome (1)
-	-	1	Familial cancer of breast (1)
-	-	1	Hereditary cancer-predisposing syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.5
DANN	Benign	0.77
PhyloP100		1.3
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: rs924117395; hg19: chr11-108196281;