16-88813828-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000268695.10(GALNS):​c.*611A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.265 in 156,244 control chromosomes in the GnomAD database, including 5,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.27 ( 5625 hom., cov: 33)
Exomes 𝑓: 0.22 ( 128 hom. )

Consequence

GALNS
ENST00000268695.10 3_prime_UTR

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.97
Variant links:
Genes affected
GALNS (HGNC:4122): (galactosamine (N-acetyl)-6-sulfatase) This gene encodes N-acetylgalactosamine-6-sulfatase which is a lysosomal exohydrolase required for the degradation of the glycosaminoglycans, keratan sulfate, and chondroitin 6-sulfate. Sequence alterations including point, missense and nonsense mutations, as well as those that affect splicing, result in a deficiency of this enzyme. Deficiencies of this enzyme lead to Morquio A syndrome, a lysosomal storage disorder. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.93).
BP6
Variant 16-88813828-T-C is Benign according to our data. Variant chr16-88813828-T-C is described in ClinVar as [Benign]. Clinvar id is 321170.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GALNSNM_000512.5 linkuse as main transcriptc.*611A>G 3_prime_UTR_variant 14/14 ENST00000268695.10 NP_000503.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GALNSENST00000268695.10 linkuse as main transcriptc.*611A>G 3_prime_UTR_variant 14/141 NM_000512.5 ENSP00000268695 P1
GALNSENST00000562593.5 linkuse as main transcriptn.5589A>G non_coding_transcript_exon_variant 12/121
GALNSENST00000567525.5 linkuse as main transcriptc.*1651A>G 3_prime_UTR_variant, NMD_transcript_variant 12/122 ENSP00000454484

Frequencies

GnomAD3 genomes
AF:
0.266
AC:
40397
AN:
152024
Hom.:
5620
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.253
Gnomad AMI
AF:
0.442
Gnomad AMR
AF:
0.267
Gnomad ASJ
AF:
0.263
Gnomad EAS
AF:
0.532
Gnomad SAS
AF:
0.213
Gnomad FIN
AF:
0.266
Gnomad MID
AF:
0.285
Gnomad NFE
AF:
0.253
Gnomad OTH
AF:
0.292
GnomAD4 exome
AF:
0.223
AC:
913
AN:
4102
Hom.:
128
Cov.:
0
AF XY:
0.221
AC XY:
471
AN XY:
2134
show subpopulations
Gnomad4 AFR exome
AF:
0.292
Gnomad4 AMR exome
AF:
0.256
Gnomad4 ASJ exome
AF:
0.250
Gnomad4 EAS exome
AF:
0.448
Gnomad4 SAS exome
AF:
0.178
Gnomad4 FIN exome
AF:
0.156
Gnomad4 NFE exome
AF:
0.206
Gnomad4 OTH exome
AF:
0.279
GnomAD4 genome
AF:
0.266
AC:
40431
AN:
152142
Hom.:
5625
Cov.:
33
AF XY:
0.267
AC XY:
19862
AN XY:
74378
show subpopulations
Gnomad4 AFR
AF:
0.253
Gnomad4 AMR
AF:
0.267
Gnomad4 ASJ
AF:
0.263
Gnomad4 EAS
AF:
0.532
Gnomad4 SAS
AF:
0.213
Gnomad4 FIN
AF:
0.266
Gnomad4 NFE
AF:
0.253
Gnomad4 OTH
AF:
0.291
Alfa
AF:
0.257
Hom.:
1841
Bravo
AF:
0.270
Asia WGS
AF:
0.329
AC:
1145
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Adenine phosphoribosyltransferase deficiency Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Mucopolysaccharidosis, MPS-IV-A Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Morquio syndrome Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.93
CADD
Benign
0.98
DANN
Benign
0.20

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.

Other links and lift over

dbSNP: rs1135364; hg19: chr16-88880236; API