Genetic Variant UNC80:p.Arg505Arg (chr2-209817086-C-A) – ACMG Classification: Likely_benign (-3 pts)

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001371986.1(UNC80):c.1513C>A(p.Arg505Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,399,474 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 Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

UNC80
NM_001371986.1 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.49

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 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.19).

BP6

Variant 2-209817086-C-A is Benign according to our data. Variant chr2-209817086-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2024339.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=2.49 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UNC80	NM_001371986.1 link	c.1513C>A	p.Arg505Arg	synonymous_variant	Exon 10 of 65	ENST00000673920.1	NP_001358915.1
UNC80	NM_032504.2 link	c.1513C>A	p.Arg505Arg	synonymous_variant	Exon 10 of 64		NP_115893.1	Q8N2C7-1
UNC80	NM_182587.4 link	c.1513C>A	p.Arg505Arg	synonymous_variant	Exon 10 of 63		NP_872393.3	Q8N2C7-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UNC80	ENST00000673920.1 link	c.1513C>A	p.Arg505Arg	synonymous_variant	Exon 10 of 65		NM_001371986.1	ENSP00000501211.1	A0A669KBC5
UNC80	ENST00000439458.5 link	c.1513C>A	p.Arg505Arg	synonymous_variant	Exon 10 of 64	5		ENSP00000391088.1	Q8N2C7-1
UNC80	ENST00000673951.1 link	c.1513C>A	p.Arg505Arg	synonymous_variant	Exon 10 of 64			ENSP00000501012.1	A0A669KAW8
UNC80	ENST00000272845.10 link	c.1513C>A	p.Arg505Arg	synonymous_variant	Exon 10 of 63	5		ENSP00000272845.5	Q8N2C7-7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000637

AC:

AN:

157044

Hom.:

AF XY:

0.00

AC XY:

AN XY:

83126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000439

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000143

AC:

AN:

1399474

Hom.:

Cov.:

AF XY:

0.0000130

AC XY:

AN XY:

690238

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000176

Gnomad4 OTH exome

AF:

0.0000172

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 04, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.19

CADD

Benign

6.6

DANN

Benign

0.64

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over