11-108317539-ATTTT-ATTTTT

Variant names:

• chr11-108317539-A-AT
• rs58978479
• NM_000051.4:c.6347+31dupT

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS1

The NM_000051.4(ATM):​c.6347+31dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0242 in 1,225,564 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 24)
  • Exomes 𝑓: 0.027 (0 hom.)
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.405

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

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 11-108317539-A-AT is Benign according to our data. Variant chr11-108317539-A-AT is described in ClinVar as [Likely_benign]. Clinvar id is 1209905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.0269 (29564/1100414) while in subpopulation EAS AF= 0.0342 (998/29170). AF 95% confidence interval is 0.0325. There are 0 homozygotes in gnomad4_exome. There are 14443 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4	c.6347+31dupT		intron_variant	Intron 43 of 62	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.6347+18_6347+19insT		intron_variant	Intron 43 of 62		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.00113 AC: 142 AN: 125130 Hom.: 0 Cov.: 24

Gnomad AFR AF: 0.000490

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000420

Gnomad ASJ AF: 0.00130

Gnomad EAS AF: 0.00117

Gnomad SAS AF: 0.00253

Gnomad FIN AF: 0.00108

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00157

Gnomad OTH AF: 0.00179

GnomAD4 exome AF: 0.0269 AC: 29564 AN: 1100414 Hom.: 0 Cov.: 0 AF XY: 0.0263 AC XY: 14443 AN XY: 548692

Gnomad4 AFR exome AF: 0.0102

Gnomad4 AMR exome AF: 0.0201

Gnomad4 ASJ exome AF: 0.0257

Gnomad4 EAS exome AF: 0.0342

Gnomad4 SAS exome AF: 0.0218

Gnomad4 FIN exome AF: 0.0294

Gnomad4 NFE exome AF: 0.0277

Gnomad4 OTH exome AF: 0.0293

GnomAD4 genome AF: 0.00113 AC: 142 AN: 125150 Hom.: 0 Cov.: 24 AF XY: 0.00120 AC XY: 72 AN XY: 59970

Gnomad4 AFR AF: 0.000489

Gnomad4 AMR AF: 0.000419

Gnomad4 ASJ AF: 0.00130

Gnomad4 EAS AF: 0.00118

Gnomad4 SAS AF: 0.00254

Gnomad4 FIN AF: 0.00108

Gnomad4 NFE AF: 0.00157

Gnomad4 OTH AF: 0.00178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 04, 2025

Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Ataxia-telangiectasia syndrome Benign:1

Feb 09, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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: rs58978479; hg19: chr11-108188266;