Genetic Variant NCALD:c.-123+64A>T (chr8-102124506-T-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001040630.2(NCALD):c.-123+64A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00075 ( 5 hom., cov: 5)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NCALD
NM_001040630.2 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.67

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]

NCALD links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 8-102124506-T-A is Benign according to our data. Variant chr8-102124506-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2658716.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
NCALD	NM_001040630.2 link	c.-123+64A>T	intron_variant	Intron 1 of 5	NP_001035720.1	P61601B2RB70
NCALD	XM_047422315.1 link	c.-210+64A>T	intron_variant	Intron 1 of 6	XP_047278271.1
NCALD	NM_001040624.2 link	c.-566A>T	upstream_gene_variant		NP_001035714.1	P61601B2RB70

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	Protein	UniProt
NCALD	ENST00000395923.5 link	c.-123+64A>T	intron_variant	Intron 1 of 5	5	ENSP00000379256.1	P61601
NCALD	ENST00000522206.5 link	c.-241+121A>T	intron_variant	Intron 1 of 4	4	ENSP00000429296.1	E5RIX3
NCALD	ENST00000522078.5 link	c.-210+64A>T	intron_variant	Intron 1 of 4	4	ENSP00000429162.1	E5RJA1

Frequencies

GnomAD3 genomes

AF:

0.000755

AC:

AN:

62238

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000218

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000638

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000330

Gnomad OTH

AF:

0.00134

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

Gnomad4 AFR exome

AC:

AN:

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

Gnomad4 ASJ exome

AC:

AN:

Gnomad4 EAS exome

AF:

0.00

AC:

AN:

Gnomad4 SAS exome

AF:

0.00

AC:

AN:

Gnomad4 FIN exome

AC:

AN:

Gnomad4 NFE exome

AF:

0.00

AC:

AN:

Gnomad4 Remaining exome

AF:

0.00

AC:

AN:

GnomAD4 genome

AF:

0.000755

AC:

AN:

62272

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

AN XY:

29838

show subpopulations

Gnomad4 AFR

AF:

0.000218

AC:

0.000217628

AN:

0.000217628

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.000639

AC:

0.000639386

AN:

0.000639386

Gnomad4 SAS

AF:

0.0169

AC:

0.0169214

AN:

0.0169214

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.000330

AC:

0.000330299

AN:

0.000330299

Gnomad4 OTH

AF:

0.00134

AC:

0.0013369

AN:

0.0013369

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

NCALD: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

7.7

DANN

Benign

0.37

Mutation Taster

=100/0

polymorphism

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over