rs764506673

Variant names:

• chr11-108325294-A-G
• rs764506673
• NM_000051.4:c.6573-16A>G

Your query was ambiguous. Multiple possible variants found:

• chr11-108325294-A-G
• chr11-108325294-A-T

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.6573-16A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000233 in 1,200,542 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 0.000047 (0 hom., cov: 29)
  • Exomes 𝑓: 0.000020 (0 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.86
• 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=-0.88).
• BP6: Variant 11-108325294-A-G is Benign according to our data. Variant chr11-108325294-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 254754.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.6573-16A>G		intron	N/A	NP_000042.3
	ATM	NM_001351834.2		c.6573-16A>G		intron	N/A	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.641-16223T>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.6573-16A>G		intron	N/A	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.6573-16A>G		intron	N/A	ENSP00000388058.2	Q13315
	ATM	ENST00000527805.6	TSL:1	n.*1637-16A>G		intron	N/A	ENSP00000435747.2	E9PIN0

Frequencies

GnomAD3 genomes AF: 0.0000472 AC: 6 AN: 127164 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.0000302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000278

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: 0.0000316

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000627 AC: 15 AN: 239420 AF XY: 0.0000538

Gnomad AFR exome AF: 0.0000657

Gnomad AMR exome AF: 0.000301

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000275

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000205 AC: 22 AN: 1073378 Hom.: 0 Cov.: 19 AF XY: 0.0000220 AC XY: 12 AN XY: 546112

African (AFR) AF: 0.0000808 AC: 2 AN: 24748

American (AMR) AF: 0.000216 AC: 9 AN: 41640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22422

East Asian (EAS) AF: 0.0000294 AC: 1 AN: 34016

South Asian (SAS) AF: 0.0000133 AC: 1 AN: 75024

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48756

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4596

European-Non Finnish (NFE) AF: 0.0000116 AC: 9 AN: 775936

Other (OTH) AF: 0.00 AC: 0 AN: 46240

GnomAD4 genome AF: 0.0000472 AC: 6 AN: 127164 Hom.: 0 Cov.: 29 AF XY: 0.0000336 AC XY: 2 AN XY: 59610

African (AFR) AF: 0.0000302 AC: 1 AN: 33072

American (AMR) AF: 0.000278 AC: 3 AN: 10806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3338

East Asian (EAS) AF: 0.00 AC: 0 AN: 4314

South Asian (SAS) AF: 0.00 AC: 0 AN: 4020

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5574

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 166

European-Non Finnish (NFE) AF: 0.0000316 AC: 2 AN: 63358

Other (OTH) AF: 0.00 AC: 0 AN: 1654

Alfa AF: 0.0000480 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Hereditary cancer-predisposing syndrome (2)
-	-	1	Ataxia-telangiectasia syndrome (1)
-	-	1	Familial cancer of breast (1)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.027
DANN	Benign	0.26
PhyloP100		-1.9
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: rs764506673; hg19: chr11-108196021;