11-11353382-T-C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198516.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT18	NM_198516.3	MANE Select	c.1093-12378A>G		intron	N/A	NP_940918.2	Q6P9A2-1
	GALNT18	NM_001363464.2		c.1092+19133A>G		intron	N/A	NP_001350393.1
	CSNK2A3	NM_001256686.2	MANE Select	c.-263A>G		upstream_gene	N/A	NP_001243615.1	Q8NEV1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GALNT18	ENST00000227756.5	TSL:1 MANE Select	c.1093-12378A>G		intron	N/A	ENSP00000227756.4	Q6P9A2-1
	GALNT18	ENST00000958463.1		c.1093-12378A>G		intron	N/A	ENSP00000628522.1
	GALNT18	ENST00000878654.1		c.1093-12378A>G		intron	N/A	ENSP00000548713.1

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

African (AFR) AF: 0.837 AC: 10134 AN: 12110

American (AMR) AF: 0.982 AC: 15842 AN: 16126

Ashkenazi Jewish (ASJ) AF: 0.995 AC: 13079 AN: 13144

East Asian (EAS) AF: 1.00 AC: 29336 AN: 29336

South Asian (SAS) AF: 0.999 AC: 42010 AN: 42050

European-Finnish (FIN) AF: 1.00 AC: 27799 AN: 27806

Middle Eastern (MID) AF: 0.977 AC: 1830 AN: 1874

European-Non Finnish (NFE) AF: 0.998 AC: 260178 AN: 260628

Other (OTH) AF: 0.982 AC: 24365 AN: 24806

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

African (AFR) AF: 0.844 AC: 35019 AN: 41504

American (AMR) AF: 0.972 AC: 14879 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.993 AC: 3447 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5179 AN: 5180

South Asian (SAS) AF: 0.999 AC: 4819 AN: 4822

European-Finnish (FIN) AF: 1.00 AC: 10613 AN: 10614

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67933 AN: 68036

Other (OTH) AF: 0.956 AC: 2022 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.2
DANN	Benign	0.64
PhyloP100		0.43
PromoterAI		-0.036	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2129523; hg19: chr11-11374929;