Variant 13-101068677-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_052867.4(NALCN):c.4330+18A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,563,004 control chromosomes in the GnomAD database, including 57,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6417 hom., cov: 32)

Exomes 𝑓: 0.26 ( 50734 hom. )

Consequence

NALCN
NM_052867.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.902

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 13-101068677-T-C is Benign according to our data. Variant chr13-101068677-T-C is described in ClinVar as [Benign]. Clinvar id is 262262.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-101068677-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NALCN	NM_052867.4 linkuse as main transcript	c.4330+18A>G		intron_variant		ENST00000251127.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NALCN	ENST00000251127.11 linkuse as main transcript	c.4330+18A>G		intron_variant		1	NM_052867.4	P1	Q8IZF0-1

Frequencies

GnomAD3 genomes

AF:

0.278

AC:

42302

AN:

151898

Hom.:

6416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.359

Gnomad AMI

AF:

0.320

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.00616

Gnomad SAS

AF:

0.178

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.280

Gnomad OTH

AF:

0.271

GnomAD3 exomes

AF:

0.231

AC:

50604

AN:

219412

Hom.:

6756

AF XY:

0.230

AC XY:

27398

AN XY:

119150

show subpopulations

Gnomad AFR exome

AF:

0.356

Gnomad AMR exome

AF:

0.130

Gnomad ASJ exome

AF:

0.300

Gnomad EAS exome

AF:

0.00437

Gnomad SAS exome

AF:

0.173

Gnomad FIN exome

AF:

0.245

Gnomad NFE exome

AF:

0.278

Gnomad OTH exome

AF:

0.238

GnomAD4 exome

AF:

0.261

AC:

367970

AN:

1410988

Hom.:

50734

Cov.:

AF XY:

0.258

AC XY:

180588

AN XY:

698722

show subpopulations

Gnomad4 AFR exome

AF:

0.358

Gnomad4 AMR exome

AF:

0.138

Gnomad4 ASJ exome

AF:

0.298

Gnomad4 EAS exome

AF:

0.00283

Gnomad4 SAS exome

AF:

0.172

Gnomad4 FIN exome

AF:

0.247

Gnomad4 NFE exome

AF:

0.278

Gnomad4 OTH exome

AF:

0.254

GnomAD4 genome

AF:

0.278

AC:

42325

AN:

152016

Hom.:

6417

Cov.:

AF XY:

0.270

AC XY:

20032

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.358

Gnomad4 AMR

AF:

0.196

Gnomad4 ASJ

AF:

0.301

Gnomad4 EAS

AF:

0.00618

Gnomad4 SAS

AF:

0.177

Gnomad4 FIN

AF:

0.247

Gnomad4 NFE

AF:

0.280

Gnomad4 OTH

AF:

0.272

Alfa

AF:

0.276

Hom.:

6281

Bravo

AF:

0.278

Asia WGS

AF:

0.138

AC:

481

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

Cadd

Benign

1.8

Dann

Benign

0.60

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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.

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