5-154294819-T-A

Variant summary

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

The NM_198321.4(GALNT10):c.163T>A(p.Ser55Thr) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: GALNT10 NM_198321.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.290

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]

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=0.07388088).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GALNT10	NM_198321.4	c.163T>A	p.Ser55Thr	missense_variant	2/12	ENST00000297107.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GALNT10	ENST00000297107.11	c.163T>A	p.Ser55Thr	missense_variant	2/12	1	NM_198321.4	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Nov 22, 2023

The c.163T>A (p.S55T) alteration is located in exon 2 (coding exon 2) of the GALNT10 gene. This alteration results from a T to A substitution at nucleotide position 163, causing the serine (S) at amino acid position 55 to be replaced by a threonine (T). 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	0.069
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
Cadd	Benign	11
Dann	Benign	0.83
Eigen	Benign	-0.78
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.60	T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.074	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;N
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.040	N;N;N
REVEL	Benign	0.046
Sift	Benign	0.61	T;T;T
Sift4G	Benign	0.57	T;T;T
Polyphen		0.095	B;B;.
Vest4		0.28
MutPred		0.16		Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);Gain of loop (P = 0.1069);
MVP		0.48
MPC		0.37
ClinPred		0.10	T
GERP RS		3.2
Varity_R		0.022
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1754248604; hg19: chr5-153674379;