chr18-26916765-C-A

Variant names:

• chr18-26916765-C-A
• rs1489712289
• NM_031422.6:c.826G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_031422.6(CHST9):​c.826G>T​(p.Ala276Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,628 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: CHST9 NM_031422.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.557
• Publications: 0 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.

• PM2: Very rare variant in population databases, with high coverage

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.826G>T	p.Ala276Ser	missense	Exon 6 of 6	NP_113610.2	Q7L1S5-1
	CHST9	NM_001398493.1		c.826G>T	p.Ala276Ser	missense	Exon 5 of 5	NP_001385422.1	Q7L1S5-1
	CHST9	NM_001256316.2		c.*563G>T		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.826G>T	p.Ala276Ser	missense	Exon 6 of 6	ENSP00000480991.1	Q7L1S5-1
	CHST9	ENST00000581714.5	TSL:1	c.826G>T	p.Ala276Ser	missense	Exon 5 of 5	ENSP00000462852.1	Q7L1S5-1
	AQP4-AS1	ENST00000578701.5	TSL:1	n.55-7995C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000274 AC: 4 AN: 1461628 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727112

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44720

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 39688

South Asian (SAS) AF: 0.00 AC: 0 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.00000360 AC: 4 AN: 1111850

Other (OTH) AF: 0.00 AC: 0 AN: 60386

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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	Benign	0.21
BayesDel_addAF	Uncertain	0.032	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.48	T
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.54
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.030	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Benign	-0.29	T
MutationAssessor	Benign	1.5	L
PhyloP100		0.56
PrimateAI	Benign	0.45	T
Sift4G	Benign	0.071	T
Polyphen		0.83	P
Vest4		0.45
MutPred		0.75		Gain of MoRF binding (P = 0.155)
MVP		0.84
ClinPred		0.84	D
GERP RS		6.2
Varity_R		0.10
gMVP		0.53

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: rs1489712289; hg19: chr18-24496729;