NM_001371986.1:c.92+7G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001371986.1(UNC80):c.92+7G>A variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00676 in 1,536,440 control chromosomes in the GnomAD database, including 58 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0045 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 54 hom. )

Consequence

UNC80
NM_001371986.1 splice_region, intron

Scores

Splicing: ADA: 0.002059

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 4.98

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 Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 2-209772171-G-A is Benign according to our data. Variant chr2-209772171-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 710314.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-209772171-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00446 (676/151434) while in subpopulation NFE AF= 0.00777 (526/67702). AF 95% confidence interval is 0.00722. There are 4 homozygotes in gnomad4. There are 300 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
UNC80	NM_001371986.1 link	c.92+7G>A	splice_region_variant, intron_variant	Intron 1 of 64	ENST00000673920.1	NP_001358915.1
UNC80	NM_032504.2 link	c.92+7G>A	splice_region_variant, intron_variant	Intron 1 of 63		NP_115893.1	Q8N2C7-1
UNC80	NM_182587.4 link	c.92+7G>A	splice_region_variant, intron_variant	Intron 1 of 62		NP_872393.3	Q8N2C7-7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UNC80	ENST00000673920.1 link	c.92+7G>A		splice_region_variant, intron_variant	Intron 1 of 64		NM_001371986.1	ENSP00000501211.1		A0A669KBC5

Frequencies

GnomAD3 genomes

AF:

0.00445

AC:

674

AN:

151326

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00309

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00208

Gnomad FIN

AF:

0.00355

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00777

Gnomad OTH

AF:

0.00338

GnomAD3 exomes

AF:

0.00397

AC:

528

AN:

133046

Hom.:

AF XY:

0.00403

AC XY:

291

AN XY:

72206

show subpopulations

Gnomad AFR exome

AF:

0.000971

Gnomad AMR exome

AF:

0.00123

Gnomad ASJ exome

AF:

0.000255

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00132

Gnomad FIN exome

AF:

0.00444

Gnomad NFE exome

AF:

0.00813

Gnomad OTH exome

AF:

0.00492

GnomAD4 exome

AF:

0.00701

AC:

9714

AN:

1385006

Hom.:

Cov.:

AF XY:

0.00681

AC XY:

4655

AN XY:

683158

show subpopulations

Gnomad4 AFR exome

AF:

0.000962

Gnomad4 AMR exome

AF:

0.00153

Gnomad4 ASJ exome

AF:

0.000648

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00172

Gnomad4 FIN exome

AF:

0.00430

Gnomad4 NFE exome

AF:

0.00829

Gnomad4 OTH exome

AF:

0.00662

GnomAD4 genome

AF:

0.00446

AC:

676

AN:

151434

Hom.:

Cov.:

AF XY:

0.00406

AC XY:

300

AN XY:

73950

show subpopulations

Gnomad4 AFR

AF:

0.00113

Gnomad4 AMR

AF:

0.00309

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00355

Gnomad4 NFE

AF:

0.00777

Gnomad4 OTH

AF:

0.00334

Alfa

AF:

0.00552

Hom.:

Bravo

AF:

0.00447

Asia WGS

AF:

0.000580

AC:

AN:

3462

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypotonia, infantile, with psychomotor retardation and characteristic facies 2

Benign:2

Jan 01, 2019

Institute of Human Genetics, University of Leipzig Medical Center

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 14, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

UNC80: BP4, BS2 -

UNC80-related disorder

Benign:1

Mar 25, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

DANN

Benign

0.96

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0021

dbscSNV1_RF

Benign

0.054

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