NM_000512.5:c.318C>G

Variant names:

• chr16-88841898-G-C
• NM_000512.5:c.318C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000512.5(GALNS):​c.318C>G​(p.Asn106Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N106N) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GALNS NM_000512.5 missense, splice_region
• Scores: Splicing: ADA: 0.003320
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.902

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNS	NM_000512.5	c.318C>G	p.Asn106Lys	missense_variant, splice_region_variant	Exon 3 of 14	ENST00000268695.10	NP_000503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNS	ENST00000268695.10	c.318C>G	p.Asn106Lys	missense_variant, splice_region_variant	Exon 3 of 14	1	NM_000512.5	ENSP00000268695.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.052	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	14
DANN	Benign	0.82
DEOGEN2	Uncertain	0.74	D;.
Eigen	Benign	-0.14
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.35	N
LIST_S2	Uncertain	0.96	D;D
M_CAP	Uncertain	0.27	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	1.2	L;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-2.3	N;D
REVEL	Uncertain	0.54
Sift	Benign	0.35	T;T
Sift4G	Benign	0.36	T;.
Polyphen		1.0	D;.
Vest4		0.81
MutPred		0.56		Gain of ubiquitination at N106 (P = 0.0198);.;
MVP		0.99
MPC		0.54
ClinPred		0.93	D
GERP RS		-2.8
Varity_R		0.36
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0033
dbscSNV1_RF	Benign	0.22
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr16-88908306;