Variant rs1289556 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_052867.4(NALCN):c.4416A>C(p.Ile1472=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,610,586 control chromosomes in the GnomAD database, including 114,351 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.44 ( 17334 hom., cov: 33)

Exomes 𝑓: 0.36 ( 97017 hom. )

Consequence

NALCN
NM_052867.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.08

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 13-101067948-T-G is Benign according to our data. Variant chr13-101067948-T-G is described in ClinVar as [Benign]. Clinvar id is 262263.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-101067948-T-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=2.08 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.708 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.4416A>C	p.Ile1472=	synonymous_variant	39/44	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.4416A>C	p.Ile1472=	synonymous_variant	39/44	1	NM_052867.4	ENSP00000251127	P1	Q8IZF0-1

Frequencies

GnomAD3 genomes

AF:

0.443

AC:

67239

AN:

151916

Hom.:

17302

Cov.:

show subpopulations

Gnomad AFR

AF:

0.715

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.291

Gnomad ASJ

AF:

0.426

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.340

Gnomad FIN

AF:

0.350

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.360

Gnomad OTH

AF:

0.407

GnomAD3 exomes

AF:

0.341

AC:

85333

AN:

250328

Hom.:

16871

AF XY:

0.340

AC XY:

46007

AN XY:

135212

show subpopulations

Gnomad AFR exome

AF:

0.719

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.424

Gnomad EAS exome

AF:

0.125

Gnomad SAS exome

AF:

0.336

Gnomad FIN exome

AF:

0.354

Gnomad NFE exome

AF:

0.360

Gnomad OTH exome

AF:

0.342

GnomAD4 exome

AF:

0.356

AC:

518861

AN:

1458552

Hom.:

97017

Cov.:

AF XY:

0.355

AC XY:

257469

AN XY:

725648

show subpopulations

Gnomad4 AFR exome

AF:

0.728

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.422

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.333

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.358

Gnomad4 OTH exome

AF:

0.367

GnomAD4 genome

AF:

0.443

AC:

67305

AN:

152034

Hom.:

17334

Cov.:

AF XY:

0.433

AC XY:

32215

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.714

Gnomad4 AMR

AF:

0.290

Gnomad4 ASJ

AF:

0.426

Gnomad4 EAS

AF:

0.134

Gnomad4 SAS

AF:

0.337

Gnomad4 FIN

AF:

0.350

Gnomad4 NFE

AF:

0.360

Gnomad4 OTH

AF:

0.408

Alfa

AF:

0.378

Hom.:

19319

Bravo

AF:

0.446

Asia WGS

AF:

0.292

AC:

1013

AN:

3478

EpiCase

AF:

0.360

EpiControl

AF:

0.357

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 03, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

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

-0.48

CADD

Benign

7.1

DANN

Benign

0.80

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