rs562264493

Variant names:

• chr11-108331530-C-T
• rs562264493
• NM_000051.4:c.7602C>T

Your query was ambiguous. Multiple possible variants found:

• chr11-108331530-C-T
• chr11-108331530-C-G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_000051.4(ATM):​c.7602C>T​(p.Gly2534Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,086 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: 32)
  • Exomes 𝑓: 0.000019 (0 hom.)
• Consequence: ATM NM_000051.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.105
• Publications: 2 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 11-108331530-C-T is Benign according to our data. Variant chr11-108331530-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 232866.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.105 with no splicing effect.

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.7602C>T	p.Gly2534Gly	synonymous	Exon 51 of 63	NP_000042.3
	ATM	NM_001351834.2		c.7602C>T	p.Gly2534Gly	synonymous	Exon 52 of 64	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.641-22459G>A		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.7602C>T	p.Gly2534Gly	synonymous	Exon 51 of 63	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.7602C>T	p.Gly2534Gly	synonymous	Exon 52 of 64	ENSP00000388058.2	Q13315
	C11orf65	ENST00000615746.4	TSL:1	c.*1307G>A		3_prime_UTR	Exon 13 of 13	ENSP00000483537.1	Q8NCR3-1

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151252 Hom.: 0 Cov.: 32

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: 0.000419

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000637 AC: 16 AN: 251134 AF XY: 0.0000884

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000192 AC: 28 AN: 1460718 Hom.: 0 Cov.: 31 AF XY: 0.0000234 AC XY: 17 AN XY: 726646

African (AFR) AF: 0.00 AC: 0 AN: 33456

American (AMR) AF: 0.00 AC: 0 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26098

East Asian (EAS) AF: 0.00 AC: 0 AN: 39582

South Asian (SAS) AF: 0.000267 AC: 23 AN: 86064

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53300

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5736

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111472

Other (OTH) AF: 0.0000663 AC: 4 AN: 60344

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 151368 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 73902

African (AFR) AF: 0.00 AC: 0 AN: 41230

American (AMR) AF: 0.00 AC: 0 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000419 AC: 2 AN: 4772

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10378

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67842

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Asia WGS AF: 0.000289 AC: 1 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Familial cancer of breast (2)
-	-	2	Hereditary cancer-predisposing syndrome (2)
-	-	1	Ataxia-telangiectasia syndrome (1)
-	-	1	Breast and/or ovarian cancer (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	7.4
DANN	Benign	0.75
PhyloP100		-0.10
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=93/7	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: rs562264493; hg19: chr11-108202257;