chr11-108365552-A-G

Variant names:

• chr11-108365552-A-G
• rs55900855
• NM_000051.4:c.*44A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_000051.4(ATM):​c.*44A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,590,728 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (9 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (7 hom.)
• Consequence: ATM NM_000051.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.0930
• Publications: 4 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 11-108365552-A-G is Benign according to our data. Variant chr11-108365552-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 302256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00586 (893/152286) while in subpopulation AFR AF = 0.0174 (725/41558). AF 95% confidence interval is 0.0164. There are 9 homozygotes in GnomAd4. There are 409 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AD,AR gene

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.*44A>G		3_prime_UTR	Exon 63 of 63	NP_000042.3
	ATM	NM_001351834.2		c.*44A>G		3_prime_UTR	Exon 64 of 64	NP_001338763.1
	C11orf65	NM_001330368.2		c.640+20368T>C		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.*44A>G		3_prime_UTR	Exon 63 of 63	ENSP00000501606.1
	ATM	ENST00000452508.7	TSL:1	c.*44A>G		3_prime_UTR	Exon 64 of 64	ENSP00000388058.2
	C11orf65	ENST00000615746.4	TSL:1	c.*2-9443T>C		intron	N/A	ENSP00000483537.1

Frequencies

GnomAD3 genomes AF: 0.00588 AC: 894 AN: 152168 Hom.: 9 Cov.: 31

Gnomad AFR AF: 0.0175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000829

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.00574

GnomAD2 exomes AF: 0.00247 AC: 536 AN: 217182 AF XY: 0.00195

Gnomad AFR exome AF: 0.0180

Gnomad AMR exome AF: 0.00177

Gnomad ASJ exome AF: 0.0147

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000633

Gnomad OTH exome AF: 0.00217

GnomAD4 exome AF: 0.00118 AC: 1698 AN: 1438442 Hom.: 7 Cov.: 29 AF XY: 0.00112 AC XY: 801 AN XY: 714374

African (AFR) AF: 0.0182 AC: 596 AN: 32784

American (AMR) AF: 0.00219 AC: 91 AN: 41536

Ashkenazi Jewish (ASJ) AF: 0.0142 AC: 366 AN: 25772

East Asian (EAS) AF: 0.00 AC: 0 AN: 38934

South Asian (SAS) AF: 0.00117 AC: 98 AN: 84010

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52468

Middle Eastern (MID) AF: 0.00175 AC: 10 AN: 5722

European-Non Finnish (NFE) AF: 0.000360 AC: 395 AN: 1097576

Other (OTH) AF: 0.00238 AC: 142 AN: 59640

GnomAD4 genome AF: 0.00586 AC: 893 AN: 152286 Hom.: 9 Cov.: 31 AF XY: 0.00549 AC XY: 409 AN XY: 74474

African (AFR) AF: 0.0174 AC: 725 AN: 41558

American (AMR) AF: 0.00504 AC: 77 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4822

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10610

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

European-Non Finnish (NFE) AF: 0.000426 AC: 29 AN: 68028

Other (OTH) AF: 0.00568 AC: 12 AN: 2112

Alfa AF: 0.00263 Hom.: 1

Bravo AF: 0.00714

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.7
DANN	Benign	0.42
PhyloP100		-0.093
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: rs55900855; hg19: chr11-108236279;