11-11327095-C-A

Position:

• chr11-11327095-C-A

Variant summary

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

The NM_198516.3(GALNT18):​c.1503G>T​(p.Met501Ile) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GALNT18 NM_198516.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.77

Genes affected

GALNT18 (HGNC:30488): (polypeptide N-acetylgalactosaminyltransferase 18) Enables polypeptide N-acetylgalactosaminyltransferase activity. Involved in protein O-linked glycosylation. Predicted to be located in Golgi membrane. Predicted to be integral component of membrane. Predicted to be active in Golgi apparatus. [provided by Alliance of Genome Resources, Apr 2022]

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/exons	MANE	Protein	UniProt
GALNT18	NM_198516.3	c.1503G>T	p.Met501Ile	missense_variant	9/11	ENST00000227756.5	NP_940918.2
GALNT18	NM_001363464.2	c.1317G>T	p.Met439Ile	missense_variant	8/10		NP_001350393.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GALNT18	ENST00000227756.5	c.1503G>T	p.Met501Ile	missense_variant	9/11	1	NM_198516.3	ENSP00000227756.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

Oct 01, 2024

The c.1503G>T (p.M501I) alteration is located in exon 9 (coding exon 9) of the GALNT18 gene. This alteration results from a G to T substitution at nucleotide position 1503, causing the methionine (M) at amino acid position 501 to be replaced by an isoleucine (I). 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	Pathogenic	0.87
BayesDel_addAF	Benign	-0.021	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.040	T
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.014	T
MetaRNN	Uncertain	0.49	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.0	N
REVEL	Benign	0.087
Sift	Benign	0.075	T
Sift4G	Benign	0.32	T
Polyphen		0.13	B
Vest4		0.72
MutPred		0.48		Gain of catalytic residue at P503 (P = 0.0275);
MVP		0.44
MPC		0.47
ClinPred		0.91	D
GERP RS		5.8
Varity_R		0.24
gMVP		0.44

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: rs1051339106; hg19: chr11-11348642;