Variant rs17582557 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.1836A>G(p.Lys612=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0475 in 1,581,280 control chromosomes in the GnomAD database, including 2,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 151 hom., cov: 33)

Exomes 𝑓: 0.049 ( 1880 hom. )

Consequence

NALCN
NM_052867.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 5.10

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=-0.5).

BP6

Variant 13-101176303-T-C is Benign according to our data. Variant chr13-101176303-T-C is described in ClinVar as [Benign]. Clinvar id is 262251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0515 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NALCN	NM_052867.4 linkuse as main transcript	c.1836A>G	p.Lys612=	synonymous_variant	15/44	ENST00000251127.11	NP_443099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NALCN	ENST00000251127.11 linkuse as main transcript	c.1836A>G	p.Lys612=	synonymous_variant	15/44	1	NM_052867.4	ENSP00000251127	P1	Q8IZF0-1

Frequencies

GnomAD3 genomes

AF:

0.0374

AC:

5684

AN:

152162

Hom.:

151

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00970

Gnomad AMI

AF:

0.180

Gnomad AMR

AF:

0.0300

Gnomad ASJ

AF:

0.0620

Gnomad EAS

AF:

0.000962

Gnomad SAS

AF:

0.0151

Gnomad FIN

AF:

0.0639

Gnomad MID

AF:

0.0506

Gnomad NFE

AF:

0.0530

Gnomad OTH

AF:

0.0330

GnomAD3 exomes

AF:

0.0429

AC:

9582

AN:

223590

Hom.:

263

AF XY:

0.0437

AC XY:

5317

AN XY:

121558

show subpopulations

Gnomad AFR exome

AF:

0.00776

Gnomad AMR exome

AF:

0.0374

Gnomad ASJ exome

AF:

0.0613

Gnomad EAS exome

AF:

0.000315

Gnomad SAS exome

AF:

0.0160

Gnomad FIN exome

AF:

0.0668

Gnomad NFE exome

AF:

0.0549

Gnomad OTH exome

AF:

0.0577

GnomAD4 exome

AF:

0.0486

AC:

69416

AN:

1428998

Hom.:

1880

Cov.:

AF XY:

0.0483

AC XY:

34312

AN XY:

710378

show subpopulations

Gnomad4 AFR exome

AF:

0.00690

Gnomad4 AMR exome

AF:

0.0353

Gnomad4 ASJ exome

AF:

0.0588

Gnomad4 EAS exome

AF:

0.000186

Gnomad4 SAS exome

AF:

0.0169

Gnomad4 FIN exome

AF:

0.0624

Gnomad4 NFE exome

AF:

0.0535

Gnomad4 OTH exome

AF:

0.0446

GnomAD4 genome

AF:

0.0373

AC:

5682

AN:

152282

Hom.:

151

Cov.:

AF XY:

0.0369

AC XY:

2750

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.00967

Gnomad4 AMR

AF:

0.0299

Gnomad4 ASJ

AF:

0.0620

Gnomad4 EAS

AF:

0.000965

Gnomad4 SAS

AF:

0.0151

Gnomad4 FIN

AF:

0.0639

Gnomad4 NFE

AF:

0.0530

Gnomad4 OTH

AF:

0.0326

Alfa

AF:

0.0502

Hom.:

Bravo

AF:

0.0343

Asia WGS

AF:

0.0120

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.72

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.

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