Genetic Variant UNC80:p.Glu1382Lys (chr2-209888128-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001371986.1(UNC80):c.4144G>A(p.Glu1382Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000572 in 1,399,404 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

UNC80
NM_001371986.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 9.72

Publications

1 publications found

Variant links:

Genes affected

UNC80 (HGNC:26582): (unc-80 homolog, NALCN channel complex subunit) The protein encoded by this gene is a component of a voltage-independent 'leak' ion-channel complex, in which it performs essential functions, such as serving as a bridge between two other components (sodium leak channel non-selective and UNC79) and as a scaffold for Src kinases. Leak channels play an importnat role in establishment and maintenance of resting membrane potentials in neurons. Mutations in this gene are associated with congenital infantile encephalopathy, intellectual disability and growth issues. [provided by RefSeq, Aug 2016]

UNC80 Gene-Disease associations (from GenCC):

hypotonia, infantile, with psychomotor retardation and characteristic facies 2
Inheritance: AR, AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Illumina, ClinGen
hypotonia, infantile, with psychomotor retardation and characteristic facies
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

UNC80 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.31115288).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001371986.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
UNC80	NM_001371986.1	MANE Select	c.4144G>A	p.Glu1382Lys	missense	Exon 26 of 65	NP_001358915.1
UNC80	NM_032504.2		c.4150G>A	p.Glu1384Lys	missense	Exon 26 of 64	NP_115893.1
UNC80	NM_182587.4		c.4135G>A	p.Glu1379Lys	missense	Exon 26 of 63	NP_872393.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
UNC80	ENST00000673920.1	MANE Select	c.4144G>A	p.Glu1382Lys	missense	Exon 26 of 65	ENSP00000501211.1
UNC80	ENST00000489023.5	TSL:1	n.1675G>A		non_coding_transcript_exon	Exon 12 of 37
UNC80	ENST00000439458.5	TSL:5	c.4150G>A	p.Glu1384Lys	missense	Exon 26 of 64	ENSP00000391088.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000572

AC:

AN:

1399404

Hom.:

Cov.:

AF XY:

0.00000580

AC XY:

AN XY:

690208

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31598

American (AMR)

AF:

0.00

AC:

AN:

35704

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49278

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00000649

AC:

AN:

1078968

Other (OTH)

AF:

0.00

AC:

AN:

58002

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.419

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.43

BayesDel_addAF

Benign

-0.075

BayesDel_noAF

Benign

-0.35

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.052

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.0041

MetaRNN

Benign

0.31

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.55

PhyloP100

9.7

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

-0.81

REVEL

Benign

0.16

Sift

Benign

0.040

Sift4G

Benign

0.10

Polyphen

0.94

Vest4

0.48

MutPred

0.32

Gain of MoRF binding (P = 0.0271)

MVP

0.26

MPC

0.83

ClinPred

0.81

GERP RS

5.5

Varity_R

0.18

gMVP

0.76

Mutation Taster

=49/51

disease causing

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over