dbSNP rs796052121: NBAS:p.Leu1055Pro (chr2-15394320-A-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_015909.4(NBAS):c.3164T>C(p.Leu1055Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L1055F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

NBAS
NM_015909.4 missense

Scores

Clinical Significance

Likely pathogenic criteria provided, single submitter P:2

Conservation

PhyloP100: 8.48

Publications

6 publications found

Variant links:

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

NBAS links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 2-15394320-A-G is Pathogenic according to our data. Variant chr2-15394320-A-G is described in ClinVar as Likely_pathogenic. ClinVar VariationId is 204584.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015909.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NBAS	NM_015909.4	MANE Select	c.3164T>C	p.Leu1055Pro	missense	Exon 28 of 52	NP_056993.2
	NBAS	NR_052013.3		n.3194T>C		non_coding_transcript_exon	Exon 28 of 51

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
NBAS	ENST00000281513.10	TSL:1 MANE Select	c.3164T>C	p.Leu1055Pro	missense	Exon 28 of 52	ENSP00000281513.5
NBAS	ENST00000442506.5	TSL:1	c.305T>C	p.Leu102Pro	missense	Exon 4 of 28	ENSP00000398411.1
NBAS	ENST00000914564.1		c.3164T>C	p.Leu1055Pro	missense	Exon 28 of 52	ENSP00000584623.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely pathogenic

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Infantile liver failure syndrome 2 (1)

Short stature-optic atrophy-Pelger-Huët anomaly syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.10

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.43

Eigen

Uncertain

0.48

Eigen_PC

Uncertain

0.55

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.40

MutationAssessor

Uncertain

2.5

PhyloP100

8.5

PrimateAI

Uncertain

0.56

PROVEAN

Pathogenic

-4.8

REVEL

Uncertain

0.52

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.98

MutPred

0.36

Gain of relative solvent accessibility (P = 0.0027)

MVP

0.32

MPC

0.30

ClinPred

0.99

GERP RS

5.5

Varity_R

0.87

gMVP

0.77

Mutation Taster

=8/92

disease causing (ClinVar)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over