NM_000051.4:c.*3072C>T

Variant names:

• chr11-108368580-C-T
• rs3092844
• NM_000051.4:c.*3072C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000051.4(ATM):​c.*3072C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0438 in 218,244 control chromosomes in the GnomAD database, including 874 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.057 (806 hom., cov: 32)
  • Exomes 𝑓: 0.013 (68 hom.)
• Consequence: ATM NM_000051.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.315
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 11-108368580-C-T is Benign according to our data. Variant chr11-108368580-C-T is described in ClinVar as Benign. ClinVar VariationId is 302292.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

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.*3072C>T		3_prime_UTR	Exon 63 of 63	NP_000042.3
	ATM	NM_001351834.2		c.*3072C>T		3_prime_UTR	Exon 64 of 64	NP_001338763.1	Q13315
	C11orf65	NM_001330368.2		c.640+17340G>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.*3072C>T		3_prime_UTR	Exon 63 of 63	ENSP00000501606.1	Q13315
	ATM	ENST00000452508.7	TSL:1	c.*3072C>T		3_prime_UTR	Exon 64 of 64	ENSP00000388058.2	Q13315
	C11orf65	ENST00000615746.4	TSL:1	c.*2-12471G>A		intron	N/A	ENSP00000483537.1	Q8NCR3-1

Frequencies

GnomAD3 genomes AF: 0.0571 AC: 8681 AN: 152096 Hom.: 804 Cov.: 32

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0254

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00125

Gnomad OTH AF: 0.0373

GnomAD4 exome AF: 0.0129 AC: 854 AN: 66030 Hom.: 68 Cov.: 0 AF XY: 0.0118 AC XY: 360 AN XY: 30620

African (AFR) AF: 0.181 AC: 555 AN: 3070

American (AMR) AF: 0.0298 AC: 60 AN: 2016

Ashkenazi Jewish (ASJ) AF: 0.0137 AC: 58 AN: 4220

East Asian (EAS) AF: 0.00 AC: 0 AN: 9516

South Asian (SAS) AF: 0.00379 AC: 2 AN: 528

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42

Middle Eastern (MID) AF: 0.0126 AC: 5 AN: 398

European-Non Finnish (NFE) AF: 0.00111 AC: 45 AN: 40690

Other (OTH) AF: 0.0232 AC: 129 AN: 5550

GnomAD4 genome AF: 0.0572 AC: 8706 AN: 152214 Hom.: 806 Cov.: 32 AF XY: 0.0550 AC XY: 4097 AN XY: 74436

African (AFR) AF: 0.195 AC: 8100 AN: 41484

American (AMR) AF: 0.0254 AC: 388 AN: 15294

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.000830 AC: 4 AN: 4820

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10608

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.00125 AC: 85 AN: 68024

Other (OTH) AF: 0.0369 AC: 78 AN: 2114

Alfa AF: 0.0168 Hom.: 153

Bravo AF: 0.0647

Asia WGS AF: 0.0120 AC: 42 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Ataxia-telangiectasia syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.43
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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: rs3092844; hg19: chr11-108239307;