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GeneBe

8-101692860-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_032041.3(NCALD):c.415C>G(p.Pro139Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)
Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

NCALD
NM_032041.3 missense

Scores

3
6
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0
Variant links:
Genes affected
NCALD (HGNC:7655): (neurocalcin delta) This gene encodes a member of the neuronal calcium sensor (NCS) family of calcium-binding proteins. The protein contains an N-terminal myristoylation signal and four EF-hand calcium binding loops. The protein is cytosolic at resting calcium levels; however, elevated intracellular calcium levels induce a conformational change that exposes the myristoyl group, resulting in protein association with membranes and partial co-localization with the perinuclear trans-golgi network. The protein is thought to be a regulator of G protein-coupled receptor signal transduction. Several alternatively spliced variants of this gene have been determined, all of which encode the same protein; additional variants may exist but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3506804).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
NCALDNM_032041.3 linkuse as main transcriptc.415C>G p.Pro139Ala missense_variant 3/4 ENST00000220931.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
NCALDENST00000220931.11 linkuse as main transcriptc.415C>G p.Pro139Ala missense_variant 3/41 NM_032041.3 P1

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251304
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135820
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000867
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000880
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461616
Hom.:
0
Cov.:
30
AF XY:
0.00000413
AC XY:
3
AN XY:
727124
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
31
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsDec 20, 2023The c.415C>G (p.P139A) alteration is located in exon 5 (coding exon 2) of the NCALD gene. This alteration results from a C to G substitution at nucleotide position 415, causing the proline (P) at amino acid position 139 to be replaced by an alanine (A). 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
0.47
BayesDel_addAF
Benign
-0.088
T
BayesDel_noAF
Benign
-0.17
Cadd
Pathogenic
26
Dann
Uncertain
0.98
DEOGEN2
Benign
0.40
T;T;T;T;T;T
Eigen
Uncertain
0.25
Eigen_PC
Uncertain
0.40
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.95
D;.;.;.;.;D
M_CAP
Benign
0.040
D
MetaRNN
Benign
0.35
T;T;T;T;T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Benign
1.6
L;L;L;L;L;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Pathogenic
-5.2
D;D;D;D;D;D
REVEL
Uncertain
0.33
Sift
Benign
0.051
T;T;T;T;T;T
Sift4G
Benign
0.098
T;T;T;T;T;T
Polyphen
0.13
B;B;B;B;B;.
Vest4
0.56
MutPred
0.18
Gain of MoRF binding (P = 0.0896);Gain of MoRF binding (P = 0.0896);Gain of MoRF binding (P = 0.0896);Gain of MoRF binding (P = 0.0896);Gain of MoRF binding (P = 0.0896);Gain of MoRF binding (P = 0.0896);
MVP
0.23
MPC
0.77
ClinPred
0.54
D
GERP RS
5.2
Varity_R
0.31
gMVP
0.69

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs752795281; hg19: chr8-102705088; API