NM_000051.4:c.4292A>C

Variant names:

• chr11-108289657-A-C
• NM_000051.4:c.4292A>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000051.4(ATM):​c.4292A>C​(p.Asn1431Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,938 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ATM NM_000051.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.01

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATM	NM_000051.4	c.4292A>C	p.Asn1431Thr	missense_variant	Exon 29 of 63	ENST00000675843.1	NP_000042.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATM	ENST00000675843.1	c.4292A>C	p.Asn1431Thr	missense_variant	Exon 29 of 63		NM_000051.4	ENSP00000501606.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459938 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726204

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000547

EpiControl AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.035	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.13	T;T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.71
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;.;D
M_CAP	Uncertain	0.087	D
MetaRNN	Uncertain	0.55	D;D;D
MetaSVM	Uncertain	-0.091	T
MutationAssessor	Uncertain	2.9	M;M;.
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.5	D;D;N
REVEL	Uncertain	0.35
Sift	Benign	0.054	T;T;T
Sift4G	Uncertain	0.049	D;D;D
Polyphen		0.93	P;P;.
Vest4		0.75
MutPred		0.26		Loss of methylation at K1434 (P = 0.0761);Loss of methylation at K1434 (P = 0.0761);.;
MVP		0.92
MPC		0.41
ClinPred		0.98	D
GERP RS		5.4
Varity_R		0.59
gMVP		0.51

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-108160384;