rs34513106

Variant names:

• chr13-101107546-G-A
• rs34513106
• NM_052867.4:c.2520C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-101107546-G-A
• chr13-101107546-G-C
• chr13-101107546-G-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_052867.4(NALCN):​c.2520C>T​(p.Val840Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00888 in 1,614,104 control chromosomes in the GnomAD database, including 124 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.013 (20 hom., cov: 33)
  • Exomes 𝑓: 0.0084 (104 hom.)
• Consequence: NALCN NM_052867.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.372

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 13-101107546-G-A is Benign according to our data. Variant chr13-101107546-G-A is described in ClinVar as [Benign]. Clinvar id is 262257.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.372 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0132 (2015/152300) while in subpopulation AFR AF= 0.0272 (1130/41562). AF 95% confidence interval is 0.0259. There are 20 homozygotes in gnomad4. There are 951 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 20 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NALCN	NM_052867.4	c.2520C>T	p.Val840Val	synonymous_variant	Exon 22 of 44	ENST00000251127.11	NP_443099.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NALCN	ENST00000251127.11	c.2520C>T	p.Val840Val	synonymous_variant	Exon 22 of 44	1	NM_052867.4	ENSP00000251127.6

Frequencies

GnomAD3 genomes AF: 0.0132 AC: 2015 AN: 152182 Hom.: 21 Cov.: 33

Gnomad AFR AF: 0.0272

Gnomad AMI AF: 0.0219

Gnomad AMR AF: 0.0100

Gnomad ASJ AF: 0.0181

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00932

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.00836

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00879 AC: 2208 AN: 251220 Hom.: 24 AF XY: 0.00880 AC XY: 1194 AN XY: 135754

Gnomad AFR exome AF: 0.0287

Gnomad AMR exome AF: 0.00550

Gnomad ASJ exome AF: 0.0216

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0105

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00841

Gnomad OTH exome AF: 0.00816

GnomAD4 exome AF: 0.00842 AC: 12314 AN: 1461804 Hom.: 104 Cov.: 31 AF XY: 0.00867 AC XY: 6302 AN XY: 727202

Gnomad4 AFR exome AF: 0.0271

Gnomad4 AMR exome AF: 0.00597

Gnomad4 ASJ exome AF: 0.0214

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00998

Gnomad4 FIN exome AF: 0.000693

Gnomad4 NFE exome AF: 0.00807

Gnomad4 OTH exome AF: 0.00980

GnomAD4 genome AF: 0.0132 AC: 2015 AN: 152300 Hom.: 20 Cov.: 33 AF XY: 0.0128 AC XY: 951 AN XY: 74458

Gnomad4 AFR AF: 0.0272

Gnomad4 AMR AF: 0.0100

Gnomad4 ASJ AF: 0.0181

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00933

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00838

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.0117 Hom.: 6

Bravo AF: 0.0144

Asia WGS AF: 0.00808 AC: 28 AN: 3478

EpiCase AF: 0.0105

EpiControl AF: 0.00990

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Aug 06, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.18
DANN	Benign	0.69

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

Other links and lift over

dbSNP: rs34513106; hg19: chr13-101759897;