11-108223054-C-A

Variant names:

• chr11-108223054-C-A
• ENST00000452508.7:c.-251C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000452508.7(ATM):​c.-251C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATM ENST00000452508.7 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.38
• Publications: 0 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]

ATM Gene-Disease associations (from GenCC):

• hereditary breast carcinoma

  Inheritance: AD Classification: DEFINITIVE Submitted by: Ambry Genetics, ClinGen
• ataxia telangiectasia

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Genomics England PanelApp, Labcorp Genetics (formerly Invitae), G2P, ClinGen, Laboratory for Molecular Medicine, Orphanet
• hereditary nonpolyposis colon cancer

  Inheritance: AD Classification: MODERATE, LIMITED Submitted by: ClinGen, Ambry Genetics
• prostate cancer

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
• sarcoma

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• familial ovarian cancer

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• gastric carcinoma

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000452508.7. 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.-163C>A		upstream_gene	N/A	NP_000042.3
	ATM	NM_001351834.2		c.-251C>A		upstream_gene	N/A	NP_001338763.1
	ATM	NM_001351835.2		c.-163C>A		upstream_gene	N/A	NP_001338764.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATM	ENST00000452508.7	TSL:1	c.-251C>A		5_prime_UTR	Exon 1 of 64	ENSP00000388058.2
	ATM	ENST00000683488.1		n.11C>A		non_coding_transcript_exon	Exon 1 of 2
	ATM	ENST00000601453.3	TSL:3	c.-1201C>A		5_prime_UTR	Exon 1 of 64	ENSP00000469471.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 55032 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 29820

African (AFR) AF: 0.00 AC: 0 AN: 1376

American (AMR) AF: 0.00 AC: 0 AN: 3408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1014

East Asian (EAS) AF: 0.00 AC: 0 AN: 2662

South Asian (SAS) AF: 0.00 AC: 0 AN: 10594

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 1796

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 158

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 31334

Other (OTH) AF: 0.00 AC: 0 AN: 2690

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Benign	0.96
PhyloP100		2.4
PromoterAI		-0.30	Neutral

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

hg19: chr11-108093781;