Variant 4-177431488-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_000027.4(AGA):c.*220G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00828 in 597,124 control chromosomes in the GnomAD database, including 102 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0073 ( 25 hom., cov: 33)

Exomes 𝑓: 0.0086 ( 77 hom. )

Consequence

AGA
NM_000027.4 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: -0.877

Variant links:

Genes affected

AGA (HGNC:318): (aspartylglucosaminidase) This gene encodes a member of the N-terminal nucleophile (Ntn) hydrolase family of proteins. The encoded preproprotein is proteolytically processed to generate alpha and beta chains that comprise the mature enzyme. This enzyme is involved in the catabolism of N-linked oligosaccharides of glycoproteins. It cleaves asparagine from N-acetylglucosamines as one of the final steps in the lysosomal breakdown of glycoproteins. Mutations in this gene are associated with the lysosomal storage disease aspartylglycosaminuria that results in progressive neurodegeneration. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is subject to proteolytic processing. [provided by RefSeq, Nov 2015]

AGA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 4-177431488-C-G is Benign according to our data. Variant chr4-177431488-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 348222.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0573 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
AGA	NM_000027.4 linkuse as main transcript	c.*220G>C	3_prime_UTR_variant	9/9	ENST00000264595.7
AGA	NM_001171988.2 linkuse as main transcript	c.*220G>C	3_prime_UTR_variant	9/9
AGA	NR_033655.2 linkuse as main transcript	n.1247G>C	non_coding_transcript_exon_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AGA	ENST00000264595.7 linkuse as main transcript	c.*220G>C		3_prime_UTR_variant	9/9	1	NM_000027.4	P1

Frequencies

GnomAD3 genomes

AF:

0.00727

AC:

1105

AN:

152044

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0383

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.00944

Gnomad SAS

AF:

0.00704

Gnomad FIN

AF:

0.0107

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00163

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.0156

AC:

1667

AN:

107080

Hom.:

AF XY:

0.0140

AC XY:

808

AN XY:

57866

show subpopulations

Gnomad AFR exome

AF:

0.00119

Gnomad AMR exome

AF:

0.0642

Gnomad ASJ exome

AF:

0.0308

Gnomad EAS exome

AF:

0.00715

Gnomad SAS exome

AF:

0.00950

Gnomad FIN exome

AF:

0.00920

Gnomad NFE exome

AF:

0.00119

Gnomad OTH exome

AF:

0.0138

GnomAD4 exome

AF:

0.00862

AC:

3836

AN:

444964

Hom.:

Cov.:

AF XY:

0.00831

AC XY:

2017

AN XY:

242758

show subpopulations

Gnomad4 AFR exome

AF:

0.00107

Gnomad4 AMR exome

AF:

0.0599

Gnomad4 ASJ exome

AF:

0.0340

Gnomad4 EAS exome

AF:

0.0154

Gnomad4 SAS exome

AF:

0.00898

Gnomad4 FIN exome

AF:

0.0121

Gnomad4 NFE exome

AF:

0.00174

Gnomad4 OTH exome

AF:

0.00827

GnomAD4 genome

AF:

0.00728

AC:

1107

AN:

152160

Hom.:

Cov.:

AF XY:

0.00848

AC XY:

631

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.00149

Gnomad4 AMR

AF:

0.0384

Gnomad4 ASJ

AF:

0.0392

Gnomad4 EAS

AF:

0.00946

Gnomad4 SAS

AF:

0.00705

Gnomad4 FIN

AF:

0.0107

Gnomad4 NFE

AF:

0.00163

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00773

Hom.:

Bravo

AF:

0.00976

Asia WGS

AF:

0.0210

AC:

AN:

3476

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Aspartylglucosaminuria

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

Cadd

Benign

0.61

Dann

Benign

0.46

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