rs4988104

Variant names:

• chr11-108325245-C-A
• rs4988104
• NM_000051.4:c.6573-65C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-108325245-C-A
• chr11-108325245-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_000051.4(ATM):​c.6573-65C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. 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: 𝑓 0.00019 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000056 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ATM NM_000051.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.387
• 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]

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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4	c.6573-65C>A		intron_variant	Intron 45 of 62	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.6573-65C>A		intron_variant	Intron 45 of 62		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes AF: 0.000185 AC: 22 AN: 118780 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000951

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000221

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000518

Gnomad SAS AF: 0.000287

Gnomad FIN AF: 0.00167

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000115

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000559 AC: 5 AN: 894502 Hom.: 0 AF XY: 0.00000430 AC XY: 2 AN XY: 465550

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 18060

American (AMR) AF: 0.00 AC: 0 AN: 30806

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20578

East Asian (EAS) AF: 0.00 AC: 0 AN: 35920

South Asian (SAS) AF: 0.00 AC: 0 AN: 66400

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40436

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4116

European-Non Finnish (NFE) AF: 0.00000785 AC: 5 AN: 637266

Other (OTH) AF: 0.00 AC: 0 AN: 40920

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000185 AC: 22 AN: 118802 Hom.: 0 Cov.: 31 AF XY: 0.000145 AC XY: 8 AN XY: 55034

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000950 AC: 3 AN: 31582

American (AMR) AF: 0.000221 AC: 2 AN: 9052

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3210

East Asian (EAS) AF: 0.000520 AC: 2 AN: 3848

South Asian (SAS) AF: 0.000288 AC: 1 AN: 3470

European-Finnish (FIN) AF: 0.00167 AC: 7 AN: 4196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 234

European-Non Finnish (NFE) AF: 0.000115 AC: 7 AN: 60848

Other (OTH) AF: 0.00 AC: 0 AN: 1552

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.2
DANN	Benign	0.53
PhyloP100		-0.39
Mutation Taster		=100/0	polymorphism

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

dbSNP: rs4988104; hg19: chr11-108195972;