11-11353382-T-C

Variant names:

• chr11-11353382-T-C
• rs2129523
• NM_198516.3:c.1093-12378A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198516.3(GALNT18):​c.1093-12378A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.982 in 580,138 control chromosomes in the GnomAD database, including 280,315 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.95 (69500 hom., cov: 32)
  • Exomes 𝑓: 0.99 (210815 hom.)
• Consequence: GALNT18 NM_198516.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.427

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]

CSNK2A3 (HGNC:2458): (casein kinase 2 alpha 3) This gene encodes a protein that is highly similar to the casein kinase II alpha protein. Casein kinase II is a serine/threonine protein kinase complex that phosphorylates numerous substrates including casein. The alpha subunit is the catalytic component of the complex. Mutations in this gene may be associated with a susceptibility to lung cancer. There are contradictory views among published reports of this gene as to whether or not it is a protein-coding gene or a processed pseudogene (PMIDs: 20625391, 20625391 and 10094393). [provided by RefSeq, Feb 2012]

ENSG00000255351 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GALNT18	NM_198516.3	c.1093-12378A>G		intron_variant	Intron 6 of 10	ENST00000227756.5	NP_940918.2
GALNT18	XM_011520071.4	c.*1100A>G		3_prime_UTR_variant	Exon 7 of 7		XP_011518373.1
GALNT18	NM_001363464.2	c.1092+19133A>G		intron_variant	Intron 6 of 9		NP_001350393.1
CSNK2A3	NM_001256686.2	c.-263A>G		upstream_gene_variant		ENST00000528848.3	NP_001243615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GALNT18	ENST00000227756.5	c.1093-12378A>G		intron_variant	Intron 6 of 10	1	NM_198516.3	ENSP00000227756.4
CSNK2A3	ENST00000528848.3	c.-263A>G		upstream_gene_variant		6	NM_001256686.2	ENSP00000473553.1
ENSG00000255351	ENST00000526867.1	n.*75T>C		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.953 AC: 144994 AN: 152140 Hom.: 69451 Cov.: 32

Gnomad AFR AF: 0.844

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.972

Gnomad ASJ AF: 0.993

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.949

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.956

GnomAD4 exome AF: 0.992 AC: 424573 AN: 427880 Hom.: 210815 Cov.: 3 AF XY: 0.993 AC XY: 224102 AN XY: 225626

Gnomad4 AFR exome AF: 0.837

Gnomad4 AMR exome AF: 0.982

Gnomad4 ASJ exome AF: 0.995

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.999

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.998

Gnomad4 OTH exome AF: 0.982

GnomAD4 genome AF: 0.953 AC: 145101 AN: 152258 Hom.: 69500 Cov.: 32 AF XY: 0.954 AC XY: 71062 AN XY: 74450

Gnomad4 AFR AF: 0.844

Gnomad4 AMR AF: 0.972

Gnomad4 ASJ AF: 0.993

Gnomad4 EAS AF: 1.00

Gnomad4 SAS AF: 0.999

Gnomad4 FIN AF: 1.00

Gnomad4 NFE AF: 0.998

Gnomad4 OTH AF: 0.956

Alfa AF: 0.971 Hom.: 10236

Bravo AF: 0.946

Asia WGS AF: 0.990 AC: 3442 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.64

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: rs2129523; hg19: chr11-11374929;