13-101398739-A-G

Position:

• chr13-101398739-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_052867.4(NALCN):​c.108+280T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.695 in 151,916 control chromosomes in the GnomAD database, including 38,344 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.69 (38344 hom., cov: 30)
• Consequence: NALCN NM_052867.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.04

Genes affected

NALCN (HGNC:19082): (sodium leak channel, non-selective) This gene encodes a voltage-independent, nonselective cation channel which belongs to a family of voltage-gated sodium and calcium channels that regulates the resting membrane potential and excitability of neurons. This family is expressed throughout the nervous system and conducts a persistent sodium leak current that contributes to tonic neuronal excitability. The encoded protein forms a channelosome complex that includes G-protein-coupled receptors, UNC-79, UNC-80, NCA localization factor-1, and src family tyrosine kinases. Naturally occurring mutations in this gene are associated with infantile neuroaxonal dystrophy, infantile hypotonia with psychomotor retardation and characteristic facies (IHPRF) syndrome, and congenital contractures of the limbs and face with hypotonia and developmental delay (CLIFAHDD) syndrome. A knockout of the orthologous gene in mice results in paralysis with a severely disrupted respiratory rhythm, and lethality within 24 hours after birth. [provided by RefSeq, Apr 2017]

NALCN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 13-101398739-A-G is Benign according to our data. Variant chr13-101398739-A-G is described in ClinVar as [Benign]. Clinvar id is 1265292.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.899 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NALCN	NM_052867.4	c.108+280T>C		intron_variant		ENST00000251127.11	NP_443099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NALCN	ENST00000251127.11	c.108+280T>C		intron_variant		1	NM_052867.4	ENSP00000251127.6

Frequencies

GnomAD3 genomes AF: 0.695 AC: 105428 AN: 151798 Hom.: 38271 Cov.: 30

Gnomad AFR AF: 0.906

Gnomad AMI AF: 0.784

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.573

Gnomad EAS AF: 0.854

Gnomad SAS AF: 0.676

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.670

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.695 AC: 105562 AN: 151916 Hom.: 38344 Cov.: 30 AF XY: 0.698 AC XY: 51779 AN XY: 74210

Gnomad4 AFR AF: 0.907

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.573

Gnomad4 EAS AF: 0.855

Gnomad4 SAS AF: 0.677

Gnomad4 FIN AF: 0.629

Gnomad4 NFE AF: 0.568

Gnomad4 OTH AF: 0.674

Alfa AF: 0.604 Hom.: 31645

Bravo AF: 0.712

Asia WGS AF: 0.766 AC: 2665 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	8.5
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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

Other links and lift over

dbSNP: rs9557635; hg19: chr13-102051090;