NM_002485.5:c.1060C>A

Variant names:

• chr8-89958789-G-T
• NM_002485.5:c.1060C>A

Variant summary

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

The NM_002485.5(NBN):​c.1060C>A​(p.Pro354Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NBN NM_002485.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.15

Genes affected

NBN (HGNC:7652): (nibrin) Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008]

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
NBN	NM_002485.5	c.1060C>A	p.Pro354Thr	missense_variant	Exon 9 of 16	ENST00000265433.8	NP_002476.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBN	ENST00000265433.8	c.1060C>A	p.Pro354Thr	missense_variant	Exon 9 of 16	1	NM_002485.5	ENSP00000265433.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.0085	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;T
Eigen	Uncertain	0.34
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.51	D;D
MetaSVM	Benign	-0.43	T
MutationAssessor	Uncertain	2.7	M;.
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.9	D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0030	D;D
Sift4G	Benign	0.14	T;T
Polyphen		1.0	D;.
Vest4		0.58
MutPred		0.25		Gain of glycosylation at P354 (P = 0.0168);.;
MVP		0.85
MPC		0.30
ClinPred		0.96	D
GERP RS		5.7
Varity_R		0.21
gMVP		0.55

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: chr8-90971017;