rs10498638

Positions:

• chr14-93468089-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001395159.1(UNC79):​c.143+298T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 152,150 control chromosomes in the GnomAD database, including 1,951 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 0.14 (1951 hom., cov: 29)
• Consequence: UNC79 NM_001395159.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.161

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC79	NM_001395159.1	c.143+298T>C		intron_variant		ENST00000695012.1	NP_001382088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC79	ENST00000695012.1	c.143+298T>C		intron_variant			NM_001395159.1	ENSP00000511643	P1

Frequencies

GnomAD3 genomes AF: 0.142 AC: 21513 AN: 152032 Hom.: 1951 Cov.: 29

Gnomad AFR AF: 0.0361

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.00289

Gnomad SAS AF: 0.154

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.145

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

GnomAD4 genome AF: 0.141 AC: 21520 AN: 152150 Hom.: 1951 Cov.: 29 AF XY: 0.141 AC XY: 10479 AN XY: 74362

Gnomad4 AFR AF: 0.0360

Gnomad4 AMR AF: 0.222

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.154

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.192

Gnomad4 OTH AF: 0.143

Alfa AF: 0.177 Hom.: 1402

Bravo AF: 0.143

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.60

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: rs10498638; hg19: chr14-93934435;