rs11865929

Variant names:

• chr16-88842710-C-A
• rs11865929
• NM_000512.5:c.240G>T

Your query was ambiguous. Multiple possible variants found:

• chr16-88842710-C-A
• chr16-88842710-C-G
• chr16-88842710-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_000512.5(GALNS):​c.240G>T​(p.Ser80Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,244 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 (★). Synonymous variant affecting the same amino acid position (i.e. S80S) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: GALNS NM_000512.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.55
• Publications: 0 publications found

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]

GALNS Gene-Disease associations (from GenCC):

• mucopolysaccharidosis type 4A

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 16-88842710-C-A is Benign according to our data. Variant chr16-88842710-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2720181.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.55 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000512.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNS	NM_000512.5	MANE Select	c.240G>T	p.Ser80Ser	synonymous	Exon 2 of 14	NP_000503.1
	GALNS	NM_001323544.2		c.258G>T	p.Ser86Ser	synonymous	Exon 3 of 15	NP_001310473.1
	GALNS	NM_001323543.2		c.-311-739G>T		intron	N/A	NP_001310472.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNS	ENST00000268695.10	TSL:1 MANE Select	c.240G>T	p.Ser80Ser	synonymous	Exon 2 of 14	ENSP00000268695.5
	GALNS	ENST00000562593.5	TSL:1	n.2915G>T		non_coding_transcript_exon	Exon 1 of 12
	GALNS	ENST00000565364.1	TSL:1	n.375G>T		non_coding_transcript_exon	Exon 3 of 6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1460244 Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1 AN XY: 726334

African (AFR) AF: 0.00 AC: 0 AN: 33464

American (AMR) AF: 0.00 AC: 0 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39676

South Asian (SAS) AF: 0.00 AC: 0 AN: 85984

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52720

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111616

Other (OTH) AF: 0.00 AC: 0 AN: 60344

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Mucopolysaccharidosis, MPS-IV-A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	0.42
DANN	Benign	0.73
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

Other links and lift over

dbSNP: rs11865929; hg19: chr16-88909118;