rs2125094035

Variant names:

• chr2-15167130-G-C
• rs2125094035
• NM_015909.4:c.7034C>G

Your query was ambiguous. Multiple possible variants found:

• chr2-15167130-G-C
• chr2-15167130-G-T

Variant summary

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

The NM_015909.4(NBAS):​c.7034C>G​(p.Ser2345Cys) variant causes a missense change involving the alteration of a 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2345Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NBAS NM_015909.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32
• Publications: 0 publications found

Genes affected

NBAS (HGNC:15625): (NBAS subunit of NRZ tethering complex) This gene encodes a protein with two leucine zipper domains, a ribosomal protein S14 signature domain and a Sec39 like domain. The protein is thought to be involved in Golgi-to-ER transport. Mutations in this gene are associated with short stature, optic nerve atrophy, and Pelger-Huet anomaly. [provided by RefSeq, Oct 2012]

NBAS Gene-Disease associations (from GenCC):

• infantile liver failure syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P
• short stature-optic atrophy-Pelger-Huët anomaly syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Illumina, Labcorp Genetics (formerly Invitae), G2P

ACMG classification

Our verdict: Uncertain_significance. The variant received 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
NBAS	NM_015909.4	c.7034C>G	p.Ser2345Cys	missense_variant	Exon 52 of 52	ENST00000281513.10	NP_056993.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NBAS	ENST00000281513.10	c.7034C>G	p.Ser2345Cys	missense_variant	Exon 52 of 52	1	NM_015909.4	ENSP00000281513.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.030
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T;T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.025	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;.
PhyloP100		9.3
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Uncertain	0.42
Sift	Uncertain	0.0050	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.81
MutPred		0.48		Loss of disorder (P = 0.0095);.;
MVP		0.63
MPC		0.28
ClinPred		0.98	D
GERP RS		5.3
Varity_R		0.41
gMVP		0.66
Mutation Taster		=32/68	disease causing

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

Other links and lift over

dbSNP: rs2125094035; hg19: chr2-15307254;