14-93519101-A-G

Position:

• chr14-93519101-A-G

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
UNC79	NM_001395159.1	c.899-4877A>G		intron_variant		ENST00000695012.1	NP_001382088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC79	ENST00000695012.1	c.899-4877A>G		intron_variant			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

Gnomad4 AFR AF: 0.262

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.651

Gnomad4 SAS AF: 0.368

Gnomad4 FIN AF: 0.356

Gnomad4 NFE AF: 0.307

Gnomad4 OTH AF: 0.273

Alfa AF: 0.197 Hom.: 488

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

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: rs12882384; hg19: chr14-93985447;