chr5-154376306-A-G

Variant names:

• chr5-154376306-A-G
• rs751467853
• NM_198321.4:c.598A>G

Variant summary

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

The NM_198321.4(GALNT10):​c.598A>G​(p.Met200Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,460,536 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000021 (0 hom.)
• Consequence: GALNT10 NM_198321.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.05

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 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
GALNT10	NM_198321.4	c.598A>G	p.Met200Val	missense_variant	Exon 5 of 12	ENST00000297107.11	NP_938080.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT10	ENST00000297107.11	c.598A>G	p.Met200Val	missense_variant	Exon 5 of 12	1	NM_198321.4	ENSP00000297107.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000399 AC: 10 AN: 250702 Hom.: 0 AF XY: 0.0000517 AC XY: 7 AN XY: 135522

Gnomad AFR exome AF: 0.0000616

Gnomad AMR exome AF: 0.0000292

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000212 AC: 31 AN: 1460536 Hom.: 0 Cov.: 30 AF XY: 0.0000261 AC XY: 19 AN XY: 726612

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.000651

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.0000497

GnomAD4 genome Cov.: 32

Alfa AF: 0.000102 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000247 AC: 3

EpiCase AF: 0.00

EpiControl AF: 0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Aug 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.598A>G (p.M200V) alteration is located in exon 5 (coding exon 5) of the GALNT10 gene. This alteration results from a A to G substitution at nucleotide position 598, causing the methionine (M) at amino acid position 200 to be replaced by a valine (V). 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	0.090
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Benign	0.83
DEOGEN2	Benign	0.079	.;T
Eigen	Benign	-0.28
Eigen_PC	Benign	0.050
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.019	T
MetaRNN	Uncertain	0.47	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	-1.1	N;N
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.21
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.047	B;B
Vest4		0.78
MutPred		0.61		Loss of MoRF binding (P = 0.1028);Loss of MoRF binding (P = 0.1028);
MVP		0.56
MPC		0.94
ClinPred		0.11	T
GERP RS		6.1
Varity_R		0.35
gMVP		0.71

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: rs751467853; hg19: chr5-153755866;