rs759429125

Variant names:

• chr14-93540715-C-G
• rs759429125
• NM_001395159.1:c.1408C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-93540715-C-G
• chr14-93540715-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001395159.1(UNC79):​c.1408C>G​(p.Arg470Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,510 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R470W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: UNC79 NM_001395159.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.19
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC79	NM_001395159.1	c.1408C>G	p.Arg470Gly	missense_variant	Exon 13 of 52	ENST00000695012.1	NP_001382088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC79	ENST00000695012.1	c.1408C>G	p.Arg470Gly	missense_variant	Exon 13 of 52		NM_001395159.1	ENSP00000511643.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461510 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727072

African (AFR) AF: 0.00 AC: 0 AN: 33468

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86240

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53352

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5558

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111986

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	.;T;.;T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.61
FATHMM_MKL	Uncertain	0.94	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.64	D;D;D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.49	.;.;N;N;.
PhyloP100		3.2
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.1	N;N;N;N;.
REVEL	Benign	0.23
Sift	Benign	0.19	T;T;T;T;.
Sift4G	Pathogenic	0.0	D;D;D;D;D
Polyphen		0.99	.;.;.;D;.
Vest4		0.74
MutPred		0.46		.;Gain of catalytic residue at L473 (P = 0.0032);Gain of catalytic residue at L473 (P = 0.0032);Gain of catalytic residue at L473 (P = 0.0032);.;
MVP		0.24
MPC		2.4
ClinPred		0.92	D
GERP RS		5.8
Varity_R		0.28
gMVP		0.61
Mutation Taster		=63/37	polymorphism

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: rs759429125; hg19: chr14-94007061;