rs10498638

Variant names:

• chr14-93468089-T-C
• rs10498638
• NM_001395159.1:c.143+298T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.88).
• 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 rank	MANE	Protein	UniProt
UNC79	NM_001395159.1	c.143+298T>C		intron_variant	Intron 2 of 51	ENST00000695012.1	NP_001382088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC79	ENST00000695012.1	c.143+298T>C		intron_variant	Intron 2 of 51		NM_001395159.1	ENSP00000511643.1

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

African (AFR) AF: 0.0360 AC: 1496 AN: 41550

American (AMR) AF: 0.222 AC: 3388 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3468

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5184

South Asian (SAS) AF: 0.154 AC: 743 AN: 4826

European-Finnish (FIN) AF: 0.169 AC: 1782 AN: 10568

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13020 AN: 67968

Other (OTH) AF: 0.143 AC: 302 AN: 2110

Alfa AF: 0.172 Hom.: 1882

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
PhyloP100		-0.16
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: rs10498638; hg19: chr14-93934435;