rs1555091083

chr11-108280970-AT-Achr11-108280970-AT-ATTchr11-108280970-AT-ATTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000051.4(ATM):c.3403-15del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000506 in 1,467,312 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00053 (1 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.301

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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 11-108280970-AT-A is Benign according to our data. Variant chr11-108280970-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 2692170.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-108280970-AT-A is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATM	NM_000051.4	c.3403-15del		intron_variant		ENST00000675843.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATM	ENST00000675843.1	c.3403-15del		intron_variant			NM_000051.4	P1

Frequencies

GnomAD3 genomes AF: 0.000181 AC: 19 AN: 105084 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000229

Gnomad SAS AF: 0.00109

Gnomad FIN AF: 0.000159

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000195

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000530 AC: 722 AN: 1362130 Hom.: 1 Cov.: 26 AF XY: 0.000539 AC XY: 367 AN XY: 680648

Gnomad4 AFR exome AF: 0.000359

Gnomad4 AMR exome AF: 0.000312

Gnomad4 ASJ exome AF: 0.000404

Gnomad4 EAS exome AF: 0.000505

Gnomad4 SAS exome AF: 0.00113

Gnomad4 FIN exome AF: 0.000258

Gnomad4 NFE exome AF: 0.000515

Gnomad4 OTH exome AF: 0.000530

GnomAD4 genome AF: 0.000190 AC: 20 AN: 105182 Hom.: 0 Cov.: 31 AF XY: 0.000177 AC XY: 9 AN XY: 50720

Gnomad4 AFR AF: 0.000184

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000229

Gnomad4 SAS AF: 0.00109

Gnomad4 FIN AF: 0.000159

Gnomad4 NFE AF: 0.000195

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000210 Hom.: 0

Bravo AF: 0.000144

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Feb 06, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs1555091083; hg19: chr11-108151697;