14-93519101-A-G

Variant names:

• chr14-93519101-A-G
• rs12882384
• NM_001395159.1:c.899-4877A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395159.1(UNC79):​c.899-4877A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 151,594 control chromosomes in the GnomAD database, including 7,533 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.31 (7533 hom., cov: 32)
• Consequence: UNC79 NM_001395159.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.649
• Publications: 5 publications found

Genes affected

UNC79 (HGNC:19966): (unc-79 homolog, NALCN channel complex subunit) The NALCN channel is responsible for Na(+) leak currents. The protein encoded by this gene, along with UNC80, is an accessory subunit of the NALCN channel that contributes to the Ca(2+) sensitivity of the channel. [provided by RefSeq, Sep 2016]

UNC79 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC79	NM_001395159.1	c.899-4877A>G		intron_variant	Intron 7 of 51	ENST00000695012.1	NP_001382088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC79	ENST00000695012.1	c.899-4877A>G		intron_variant	Intron 7 of 51		NM_001395159.1	ENSP00000511643.1

Frequencies

GnomAD3 genomes AF: 0.307 AC: 46572 AN: 151476 Hom.: 7532 Cov.: 32

Gnomad AFR AF: 0.262

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.652

Gnomad SAS AF: 0.367

Gnomad FIN AF: 0.356

Gnomad MID AF: 0.234

Gnomad NFE AF: 0.307

Gnomad OTH AF: 0.269

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.307 AC: 46615 AN: 151594 Hom.: 7533 Cov.: 32 AF XY: 0.309 AC XY: 22916 AN XY: 74068

African (AFR) AF: 0.262 AC: 10875 AN: 41464

American (AMR) AF: 0.270 AC: 4108 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1157 AN: 3464

East Asian (EAS) AF: 0.651 AC: 3353 AN: 5152

South Asian (SAS) AF: 0.368 AC: 1774 AN: 4820

European-Finnish (FIN) AF: 0.356 AC: 3735 AN: 10506

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.307 AC: 20780 AN: 67644

Other (OTH) AF: 0.273 AC: 575 AN: 2106

Alfa AF: 0.202 Hom.: 524

Bravo AF: 0.300

Asia WGS AF: 0.493 AC: 1706 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.0
DANN	Benign	0.74
PhyloP100		0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12882384; hg19: chr14-93985447;