rs9513851

Variant summary

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

The NM_052867.4(NALCN):c.3210C>T(p.Asn1070=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 1,611,716 control chromosomes in the GnomAD database, including 3,776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.063 ( 332 hom., cov: 32)

Exomes 𝑓: 0.065 ( 3444 hom. )

Consequence

NALCN
NM_052867.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.39

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 13-101095633-G-A is Benign according to our data. Variant chr13-101095633-G-A is described in ClinVar as [Benign]. Clinvar id is 262259.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.38 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.104 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.3210C>T	p.Asn1070=	synonymous_variant	28/44	ENST00000251127.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NALCN	ENST00000251127.11 linkuse as main transcript	c.3210C>T	p.Asn1070=	synonymous_variant	28/44	1	NM_052867.4	P1	Q8IZF0-1

Frequencies

GnomAD3 genomes

AF:

0.0633

AC:

9608

AN:

151756

Hom.:

330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0742

Gnomad AMI

AF:

0.0407

Gnomad AMR

AF:

0.0489

Gnomad ASJ

AF:

0.100

Gnomad EAS

AF:

0.0340

Gnomad SAS

AF:

0.112

Gnomad FIN

AF:

0.0384

Gnomad MID

AF:

0.0981

Gnomad NFE

AF:

0.0612

Gnomad OTH

AF:

0.0535

GnomAD3 exomes

AF:

0.0627

AC:

15678

AN:

249948

Hom.:

625

AF XY:

0.0670

AC XY:

9056

AN XY:

135164

show subpopulations

Gnomad AFR exome

AF:

0.0706

Gnomad AMR exome

AF:

0.0304

Gnomad ASJ exome

AF:

0.0963

Gnomad EAS exome

AF:

0.0375

Gnomad SAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.0445

Gnomad NFE exome

AF:

0.0624

Gnomad OTH exome

AF:

0.0653

GnomAD4 exome

AF:

0.0647

AC:

94412

AN:

1459842

Hom.:

3444

Cov.:

AF XY:

0.0666

AC XY:

48389

AN XY:

726226

show subpopulations

Gnomad4 AFR exome

AF:

0.0713

Gnomad4 AMR exome

AF:

0.0317

Gnomad4 ASJ exome

AF:

0.0945

Gnomad4 EAS exome

AF:

0.0334

Gnomad4 SAS exome

AF:

0.114

Gnomad4 FIN exome

AF:

0.0473

Gnomad4 NFE exome

AF:

0.0628

Gnomad4 OTH exome

AF:

0.0692

GnomAD4 genome

AF:

0.0633

AC:

9621

AN:

151874

Hom.:

332

Cov.:

AF XY:

0.0636

AC XY:

4719

AN XY:

74242

show subpopulations

Gnomad4 AFR

AF:

0.0742

Gnomad4 AMR

AF:

0.0489

Gnomad4 ASJ

AF:

0.100

Gnomad4 EAS

AF:

0.0345

Gnomad4 SAS

AF:

0.112

Gnomad4 FIN

AF:

0.0384

Gnomad4 NFE

AF:

0.0612

Gnomad4 OTH

AF:

0.0529

Alfa

AF:

0.0656

Hom.:

328

Bravo

AF:

0.0626

Asia WGS

AF:

0.0660

AC:

229

AN:

3478

EpiCase

AF:

0.0631

EpiControl

AF:

0.0644

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 15, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	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

4.7

Dann

Benign

0.68

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

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