18-26916650-C-T

Variant names:

• chr18-26916650-C-T
• rs201523792
• NM_031422.6:c.941G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_031422.6(CHST9):​c.941G>A​(p.Arg314Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0002 in 1,613,586 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: CHST9 NM_031422.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.82
• Publications: 3 publications found

Genes affected

CHST9 (HGNC:19898): (carbohydrate sulfotransferase 9) The protein encoded by this gene belongs to the sulfotransferase 2 family. It is localized to the golgi membrane, and catalyzes the transfer of sulfate to position 4 of non-reducing N-acetylgalactosamine (GalNAc) residues in both N-glycans and O-glycans. Sulfate groups on carbohydrates confer highly specific functions to glycoproteins, glycolipids, and proteoglycans, and are critical for cell-cell interaction, signal transduction, and embryonic development. Alternatively spliced transcript variants have been described for this gene. [provided by RefSeq, Aug 2011]

AQP4-AS1 (HGNC:26399): (AQP4 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.913

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_031422.6. 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
	CHST9	NM_031422.6	MANE Select	c.941G>A	p.Arg314Gln	missense	Exon 6 of 6	NP_113610.2	Q7L1S5-1
	CHST9	NM_001398493.1		c.941G>A	p.Arg314Gln	missense	Exon 5 of 5	NP_001385422.1	Q7L1S5-1
	CHST9	NM_001256316.2		c.*678G>A		3_prime_UTR	Exon 5 of 5	NP_001243245.1	Q7L1S5-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHST9	ENST00000618847.5	TSL:1 MANE Select	c.941G>A	p.Arg314Gln	missense	Exon 6 of 6	ENSP00000480991.1	Q7L1S5-1
	CHST9	ENST00000581714.5	TSL:1	c.941G>A	p.Arg314Gln	missense	Exon 5 of 5	ENSP00000462852.1	Q7L1S5-1
	AQP4-AS1	ENST00000578701.5	TSL:1	n.55-8110C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000658 AC: 10 AN: 152030 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000965 AC: 24 AN: 248810 AF XY: 0.0000815

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000178

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000213 AC: 312 AN: 1461556 Hom.: 0 Cov.: 32 AF XY: 0.000191 AC XY: 139 AN XY: 727092

African (AFR) AF: 0.0000598 AC: 2 AN: 33464

American (AMR) AF: 0.0000224 AC: 1 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000265 AC: 295 AN: 1111786

Other (OTH) AF: 0.000199 AC: 12 AN: 60386

GnomAD4 genome AF: 0.0000658 AC: 10 AN: 152030 Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6 AN XY: 74232

African (AFR) AF: 0.0000241 AC: 1 AN: 41408

American (AMR) AF: 0.000131 AC: 2 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10588

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.000146 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.000533 AC: 2

ESP6500EA AF: 0.000122 AC: 1

ExAC AF: 0.0000911 AC: 11

EpiCase AF: 0.000218

EpiControl AF: 0.000415

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.42
BayesDel_addAF	Pathogenic	0.22	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	30
DANN	Pathogenic	1.0
DEOGEN2	Pathogenic	0.80	D
Eigen	Pathogenic	0.87
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	0.33	D
MutationAssessor	Pathogenic	3.5	H
PhyloP100		5.8
PrimateAI	Uncertain	0.59	T
Sift4G	Uncertain	0.0060	D
Polyphen		1.0	D
Vest4		0.90
MVP		0.91
ClinPred		0.92	D
GERP RS		6.2
Varity_R		0.69
gMVP		0.71
Mutation Taster		=51/49	polymorphism

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: rs201523792; hg19: chr18-24496614; COSMIC: COSV99033713;