5-154329693-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198321.4(GALNT10):c.523G>C(p.Glu175Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 30)
• Consequence: GALNT10 NM_198321.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.11

Genes affected

GALNT10 (HGNC:19873): (polypeptide N-acetylgalactosaminyltransferase 10) This gene encodes a member of the GalNAc polypeptide N-acetylgalactosaminyltransferases. These enzymes catalyze the first step in the synthesis of mucin-type oligosaccharides. These proteins transfer GalNAc from UDP-GalNAc to either serine or threonine residues of polypeptide acceptors. The protein encoded by this locus may have increased catalytic activity toward glycosylated peptides compared to activity toward non-glycosylated peptides.[provided by RefSeq, Apr 2010]

SAP30L-AS1 (HGNC:26760): (SAP30L antisense RNA 1 (head to head))

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2537434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT10	NM_198321.4	c.523G>C	p.Glu175Gln	missense_variant	4/12	ENST00000297107.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT10	ENST00000297107.11	c.523G>C	p.Glu175Gln	missense_variant	4/12	1	NM_198321.4	P1
SAP30L-AS1	ENST00000658072.1	n.466C>G		non_coding_transcript_exon_variant	3/3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 30

Alfa AF: 0.0000468 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.523G>C (p.E175Q) alteration is located in exon 4 (coding exon 4) of the GALNT10 gene. This alteration results from a G to C substitution at nucleotide position 523, causing the glutamic acid (E) at amino acid position 175 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
Cadd	Benign	18
Dann	Uncertain	0.99
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.066
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.80	T;T;T
M_CAP	Benign	0.0056	T
MetaRNN	Benign	0.25	T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.15	N;N;N
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.73	N;N;N
REVEL	Benign	0.033
Sift	Benign	0.23	T;T;D
Sift4G	Benign	0.51	T;T;T
Polyphen		0.0040	B;B;B
Vest4		0.33
MutPred		0.33		Loss of glycosylation at P174 (P = 0.0678);Loss of glycosylation at P174 (P = 0.0678);Loss of glycosylation at P174 (P = 0.0678);
MVP		0.72
MPC		0.41
ClinPred		0.67	D
GERP RS		4.4
Varity_R		0.33
gMVP		0.53

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

Other links and lift over

dbSNP: rs1754813589; hg19: chr5-153709253;