rs587780779

chr8-89984543-C-Achr8-89984543-C-Gchr8-89984543-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002485.5(NBN):c.19G>T(p.Ala7Ser) variant causes a missense 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A7V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NBN NM_002485.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17825481).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NBN	NM_002485.5	c.19G>T	p.Ala7Ser	missense_variant	1/16	ENST00000265433.8
NBN	XM_011517046.2	c.19G>T	p.Ala7Ser	missense_variant	1/11
NBN	XM_047421796.1	c.19G>T	p.Ala7Ser	missense_variant	1/10
NBN	NM_001024688.3	c.-278G>T		5_prime_UTR_variant	1/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NBN	ENST00000265433.8	c.19G>T	p.Ala7Ser	missense_variant	1/16	1	NM_002485.5	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	13
Dann	Uncertain	0.98
DEOGEN2	Benign	0.055	T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.49
FATHMM_MKL	Benign	0.0044	N
LIST_S2	Benign	0.76	T;T
M_CAP	Benign	0.0076	T
MetaRNN	Benign	0.18	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.60	N;N
REVEL	Benign	0.074
Sift	Uncertain	0.0090	D;T
Sift4G	Benign	0.098	T;T
Polyphen		0.96	D;.
Vest4		0.14
MutPred		0.46		Gain of glycosylation at A7 (P = 0.0146);Gain of glycosylation at A7 (P = 0.0146);
MVP		0.53
MPC		0.14
ClinPred		0.32	T
GERP RS		2.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.0
Varity_R		0.11
gMVP		0.38

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: chr8-90996771; COSMIC: COSV105844510; COSMIC: COSV105844510;