Variant 2-209772130-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001371986.1(UNC80):c.58C>T(p.Leu20Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0236 in 1,548,676 control chromosomes in the GnomAD database, including 551 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 29 hom., cov: 31)

Exomes 𝑓: 0.024 ( 522 hom. )

Consequence

UNC80
NM_001371986.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.35

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:

UNC80 (HGNC:):

UNC80 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.36).

BP6

Variant 2-209772130-C-T is Benign according to our data. Variant chr2-209772130-C-T is described in ClinVar as [Benign]. Clinvar id is 1670291.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.35 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0163 (2473/151980) while in subpopulation NFE AF= 0.0255 (1733/67918). AF 95% confidence interval is 0.0245. There are 29 homozygotes in gnomad4. There are 1117 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UNC80	NM_001371986.1 linkuse as main transcript	c.58C>T	p.Leu20Leu	synonymous_variant	1/65	ENST00000673920.1	NP_001358915.1
UNC80	NM_032504.2 linkuse as main transcript	c.58C>T	p.Leu20Leu	synonymous_variant	1/64		NP_115893.1	Q8N2C7-1
UNC80	NM_182587.4 linkuse as main transcript	c.58C>T	p.Leu20Leu	synonymous_variant	1/63		NP_872393.3	Q8N2C7-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UNC80	ENST00000673920.1 linkuse as main transcript	c.58C>T	p.Leu20Leu	synonymous_variant	1/65		NM_001371986.1	ENSP00000501211.1		A0A669KBC5

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2472

AN:

151874

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00442

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.0250

Gnomad ASJ

AF:

0.0213

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00290

Gnomad FIN

AF:

0.00274

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0255

Gnomad OTH

AF:

0.0144

GnomAD3 exomes

AF:

0.0156

AC:

2353

AN:

150462

Hom.:

AF XY:

0.0157

AC XY:

1258

AN XY:

80218

show subpopulations

Gnomad AFR exome

AF:

0.00453

Gnomad AMR exome

AF:

0.0185

Gnomad ASJ exome

AF:

0.0169

Gnomad EAS exome

AF:

0.0000915

Gnomad SAS exome

AF:

0.00352

Gnomad FIN exome

AF:

0.00164

Gnomad NFE exome

AF:

0.0268

Gnomad OTH exome

AF:

0.0241

GnomAD4 exome

AF:

0.0244

AC:

34109

AN:

1396696

Hom.:

522

Cov.:

AF XY:

0.0239

AC XY:

16470

AN XY:

688946

show subpopulations

Gnomad4 AFR exome

AF:

0.00369

Gnomad4 AMR exome

AF:

0.0203

Gnomad4 ASJ exome

AF:

0.0164

Gnomad4 EAS exome

AF:

0.0000561

Gnomad4 SAS exome

AF:

0.00301

Gnomad4 FIN exome

AF:

0.00224

Gnomad4 NFE exome

AF:

0.0287

Gnomad4 OTH exome

AF:

0.0255

GnomAD4 genome

AF:

0.0163

AC:

2473

AN:

151980

Hom.:

Cov.:

AF XY:

0.0150

AC XY:

1117

AN XY:

74266

show subpopulations

Gnomad4 AFR

AF:

0.00441

Gnomad4 AMR

AF:

0.0249

Gnomad4 ASJ

AF:

0.0213

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00311

Gnomad4 FIN

AF:

0.00274

Gnomad4 NFE

AF:

0.0255

Gnomad4 OTH

AF:

0.0143

Alfa

AF:

0.0219

Hom.:

Bravo

AF:

0.0192

Asia WGS

AF:

0.00232

AC:

AN:

3466

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.36

CADD

Benign

8.3

DANN

Benign

0.93

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

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