19-48913071-A-T

Position:

• chr19-48913071-A-T

Variant summary

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

The NM_006184.6(NUCB1):​c.541A>T​(p.Met181Leu) 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.

• Frequency: Genomes: not found (cov: 30)
• Consequence: NUCB1 NM_006184.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.15

Genes affected

NUCB1 (HGNC:8043): (nucleobindin 1) This gene encodes a member of a small calcium-binding EF-hand protein family. The encoded protein is thought to have a key role in Golgi calcium homeostasis and Ca(2+)-regulated signal transduction events. [provided by RefSeq, Jun 2010]

NUCB1 (HGNC:):

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/exons	MANE	Protein	UniProt
NUCB1	NM_006184.6	c.541A>T	p.Met181Leu	missense_variant	6/13	ENST00000405315.9	NP_006175.2
NUCB1	XM_017026845.2	c.541A>T	p.Met181Leu	missense_variant	6/13		XP_016882334.1
NUCB1-AS1	NR_046633.1	n.189-1897T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NUCB1	ENST00000405315.9	c.541A>T	p.Met181Leu	missense_variant	6/13	1	NM_006184.6	ENSP00000385923.3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 2024

The c.541A>T (p.M181L) alteration is located in exon 6 (coding exon 5) of the NUCB1 gene. This alteration results from a A to T substitution at nucleotide position 541, causing the methionine (M) at amino acid position 181 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.45
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Uncertain	0.60	D;D;.
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.87	D;.;D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.63	D;D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.7	L;L;.
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-2.1	N;N;N
REVEL	Benign	0.25
Sift	Benign	0.065	T;T;T
Sift4G	Benign	0.26	T;T;D
Polyphen		0.0070	B;B;.
Vest4		0.68
MutPred		0.50		Loss of MoRF binding (P = 0.085);Loss of MoRF binding (P = 0.085);Loss of MoRF binding (P = 0.085);
MVP		0.40
MPC		0.27
ClinPred		0.89	D
GERP RS		5.1
Varity_R		0.41
gMVP		0.41

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: chr19-49416328;