rs3218711

Variant names:

• chr11-108365537-C-G
• rs3218711
• NM_000051.4:c.*29C>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.*29C>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 0.00679 in 1,607,046 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0060 (6 hom., cov: 32)
  • Exomes 𝑓: 0.0069 (35 hom.)
• Consequence: ATM NM_000051.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.50
• Publications: 6 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=-0.83).
• BP6: Variant 11-108365537-C-G is Benign according to our data. Variant chr11-108365537-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 302255.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.006 (913/152266) while in subpopulation EAS AF = 0.0106 (55/5184). AF 95% confidence interval is 0.00837. There are 6 homozygotes in GnomAd4. There are 418 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 6 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	NM_000051.4	MANE Select	c.*29C>G		3_prime_UTR	Exon 63 of 63	NP_000042.3
	ATM	NM_001351834.2		c.*29C>G		3_prime_UTR	Exon 64 of 64	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.640+20383G>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.*29C>G		3_prime_UTR	Exon 63 of 63	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.*29C>G		3_prime_UTR	Exon 64 of 64	ENSP00000388058.2	Q13315
	C11orf65	ENST00000615746.4	TSL:1	c.*2-9428G>C		intron	N/A	ENSP00000483537.1	Q8NCR3-1

Frequencies

GnomAD3 genomes AF: 0.00601 AC: 914 AN: 152148 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.00777

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00327

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00657

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00511 AC: 1230 AN: 240542 AF XY: 0.00486

Gnomad AFR exome AF: 0.00774

Gnomad AMR exome AF: 0.00144

Gnomad ASJ exome AF: 0.00303

Gnomad EAS exome AF: 0.0119

Gnomad FIN exome AF: 0.000612

Gnomad NFE exome AF: 0.00687

Gnomad OTH exome AF: 0.00471

GnomAD4 exome AF: 0.00687 AC: 9999 AN: 1454780 Hom.: 35 Cov.: 30 AF XY: 0.00665 AC XY: 4809 AN XY: 723404

African (AFR) AF: 0.00772 AC: 257 AN: 33294

American (AMR) AF: 0.00187 AC: 82 AN: 43800

Ashkenazi Jewish (ASJ) AF: 0.00342 AC: 89 AN: 26038

East Asian (EAS) AF: 0.00701 AC: 277 AN: 39540

South Asian (SAS) AF: 0.00139 AC: 119 AN: 85548

European-Finnish (FIN) AF: 0.000602 AC: 32 AN: 53172

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5762

European-Non Finnish (NFE) AF: 0.00776 AC: 8598 AN: 1107436

Other (OTH) AF: 0.00894 AC: 538 AN: 60190

GnomAD4 genome AF: 0.00600 AC: 913 AN: 152266 Hom.: 6 Cov.: 32 AF XY: 0.00561 AC XY: 418 AN XY: 74458

African (AFR) AF: 0.00778 AC: 323 AN: 41540

American (AMR) AF: 0.00327 AC: 50 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3470

East Asian (EAS) AF: 0.0106 AC: 55 AN: 5184

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4822

European-Finnish (FIN) AF: 0.000565 AC: 6 AN: 10614

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

European-Non Finnish (NFE) AF: 0.00657 AC: 447 AN: 68020

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00484 Hom.: 0

Bravo AF: 0.00632

Asia WGS AF: 0.00924 AC: 32 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Ataxia-telangiectasia syndrome (2)
-	-	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	-0.83
CADD	Benign	0.23
DANN	Benign	0.49
PhyloP100		-1.5
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: rs3218711; hg19: chr11-108236264; COSMIC: COSV99590269;