Menu
GeneBe

14-93528586-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_001395159.1(UNC79):c.992C>T(p.Ala331Val) variant causes a missense change. The variant allele was found at a frequency of 0.000652 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00067 ( 0 hom. )

Consequence

UNC79
NM_001395159.1 missense

Scores

3
3
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.93
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2
?
    PP2 - Missense variant in a gene that has a low rate of benign missense variation and in which missense variants are a common mechanism of disease
Missense variant where missense usually causes diseases, UNC79
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.09034422).
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 75 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
UNC79NM_001395159.1 linkuse as main transcriptc.992C>T p.Ala331Val missense_variant 9/52 ENST00000695012.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
UNC79ENST00000695012.1 linkuse as main transcriptc.992C>T p.Ala331Val missense_variant 9/52 NM_001395159.1 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000493
AC:
75
AN:
152072
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000131
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000377
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000897
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000358
AC:
90
AN:
251408
Hom.:
0
AF XY:
0.000309
AC XY:
42
AN XY:
135884
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.000173
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000323
Gnomad NFE exome
AF:
0.000660
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.000668
AC:
977
AN:
1461626
Hom.:
0
Cov.:
30
AF XY:
0.000626
AC XY:
455
AN XY:
727112
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000201
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000262
Gnomad4 NFE exome
AF:
0.000831
Gnomad4 OTH exome
AF:
0.000480
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000493
AC:
75
AN:
152190
Hom.:
0
Cov.:
33
AF XY:
0.000538
AC XY:
40
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.000193
Gnomad4 AMR
AF:
0.000131
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000377
Gnomad4 NFE
AF:
0.000897
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000727
Hom.:
0
Bravo
AF:
0.000468
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.00151
AC:
13
ExAC
?
    Exome Aggregation Consortium database
AF:
0.000395
AC:
48
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000491
EpiControl
AF:
0.000652

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsAug 09, 2021The c.461C>T (p.A154V) alteration is located in exon 9 (coding exon 6) of the UNC79 gene. This alteration results from a C to T substitution at nucleotide position 461, causing the alanine (A) at amino acid position 154 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.27
T
BayesDel_noAF
Benign
-0.22
Cadd
Uncertain
24
Dann
Pathogenic
1.0
Eigen
Uncertain
0.56
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Uncertain
0.97
D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.090
T;T;T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Pathogenic
0.87
D
PROVEAN
Benign
-1.5
N;N;N;N;.
REVEL
Benign
0.23
Sift
Benign
0.10
T;T;T;T;.
Sift4G
Pathogenic
0.0
D;D;D;D;D
Polyphen
1.0
.;.;.;D;.
Vest4
0.54
MVP
0.043
MPC
2.1
ClinPred
0.27
T
GERP RS
5.3
Varity_R
0.19
gMVP
0.58

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs150368733; hg19: chr14-93994932; COSMIC: COSV56416929; API