NM_001040630.2:c.-123+64A>G

Variant names:

• chr8-102124506-T-C
• rs13253373
• NM_001040630.2:c.-123+64A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001040630.2(NCALD):​c.-123+64A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.42 (4755 hom., cov: 5)
  • Exomes 𝑓: 0.088 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NCALD NM_001040630.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.67
• Publications: 1 publications found

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]

ENSG00000310378 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040630.2. 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
	NCALD	NM_001040630.2		c.-123+64A>G		intron	N/A	NP_001035720.1	P61601
	NCALD	NM_001040624.2		c.-566A>G		upstream_gene	N/A	NP_001035714.1	P61601
	NCALD	NM_001040625.2		c.-479A>G		upstream_gene	N/A	NP_001035715.1	P61601

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCALD	ENST00000395923.5	TSL:5	c.-123+64A>G		intron	N/A	ENSP00000379256.1	P61601
	NCALD	ENST00000522206.5	TSL:4	c.-241+121A>G		intron	N/A	ENSP00000429296.1	E5RIX3
	NCALD	ENST00000522078.5	TSL:4	c.-210+64A>G		intron	N/A	ENSP00000429162.1	E5RJA1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 23949 AN: 56354 Hom.: 4752 Cov.: 5

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.532

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.554

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.380

Gnomad FIN AF: 0.252

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.0882 AC: 3 AN: 34 Hom.: 0 Cov.: 0 AF XY: 0.0625 AC XY: 1 AN XY: 16

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.136 AC: 3 AN: 22

Other (OTH) AF: 0.00 AC: 0 AN: 2

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00000907115), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.425 AC: 23959 AN: 56384 Hom.: 4755 Cov.: 5 AF XY: 0.406 AC XY: 10989 AN XY: 27058

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.371 AC: 6158 AN: 16618

American (AMR) AF: 0.280 AC: 1457 AN: 5198

Ashkenazi Jewish (ASJ) AF: 0.554 AC: 738 AN: 1332

East Asian (EAS) AF: 0.392 AC: 1108 AN: 2826

South Asian (SAS) AF: 0.383 AC: 630 AN: 1646

European-Finnish (FIN) AF: 0.252 AC: 694 AN: 2750

Middle Eastern (MID) AF: 0.333 AC: 26 AN: 78

European-Non Finnish (NFE) AF: 0.508 AC: 12618 AN: 24824

Other (OTH) AF: 0.440 AC: 296 AN: 672

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	8.0
DANN	Benign	0.13
PhyloP100		-2.7
PromoterAI		-0.013	Neutral
Mutation Taster		=7/93	disease causing

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs13253373; hg19: chr8-103136734;