NM_031422.6:c.609A>G

Variant names:

• chr18-26916982-T-C
• rs138794390
• NM_031422.6:c.609A>G

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_031422.6(CHST9):​c.609A>G​(p.Val203Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00312 in 1,613,922 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0028 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0032 (38 hom.)
• Consequence: CHST9 NM_031422.6 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.624
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BP6: Variant 18-26916982-T-C is Benign according to our data. Variant chr18-26916982-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2648627.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.624 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 38 AR gene

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.609A>G	p.Val203Val	synonymous	Exon 6 of 6	NP_113610.2	Q7L1S5-1
	CHST9	NM_001398493.1		c.609A>G	p.Val203Val	synonymous	Exon 5 of 5	NP_001385422.1	Q7L1S5-1
	CHST9	NM_001256316.2		c.*346A>G		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.609A>G	p.Val203Val	synonymous	Exon 6 of 6	ENSP00000480991.1	Q7L1S5-1
	CHST9	ENST00000581714.5	TSL:1	c.609A>G	p.Val203Val	synonymous	Exon 5 of 5	ENSP00000462852.1	Q7L1S5-1
	AQP4-AS1	ENST00000578701.5	TSL:1	n.55-7778T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.00284 AC: 432 AN: 152124 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00433

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00933

Gnomad FIN AF: 0.00555

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00274

Gnomad OTH AF: 0.00526

GnomAD2 exomes AF: 0.00443 AC: 1100 AN: 248318 AF XY: 0.00500

Gnomad AFR exome AF: 0.000129

Gnomad AMR exome AF: 0.00249

Gnomad ASJ exome AF: 0.0192

Gnomad EAS exome AF: 0.0000556

Gnomad FIN exome AF: 0.00553

Gnomad NFE exome AF: 0.00283

Gnomad OTH exome AF: 0.00581

GnomAD4 exome AF: 0.00315 AC: 4610 AN: 1461680 Hom.: 38 Cov.: 32 AF XY: 0.00349 AC XY: 2536 AN XY: 727140

African (AFR) AF: 0.000269 AC: 9 AN: 33468

American (AMR) AF: 0.00253 AC: 113 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.0180 AC: 469 AN: 26126

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.0101 AC: 875 AN: 86248

European-Finnish (FIN) AF: 0.00517 AC: 276 AN: 53406

Middle Eastern (MID) AF: 0.00555 AC: 32 AN: 5766

European-Non Finnish (NFE) AF: 0.00232 AC: 2575 AN: 1111870

Other (OTH) AF: 0.00431 AC: 260 AN: 60388

GnomAD4 genome AF: 0.00282 AC: 429 AN: 152242 Hom.: 1 Cov.: 33 AF XY: 0.00334 AC XY: 249 AN XY: 74446

African (AFR) AF: 0.000313 AC: 13 AN: 41562

American (AMR) AF: 0.00432 AC: 66 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3468

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00892 AC: 43 AN: 4820

European-Finnish (FIN) AF: 0.00555 AC: 59 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00272 AC: 185 AN: 67992

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00355 Hom.: 4

Bravo AF: 0.00260

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.00311

EpiControl AF: 0.00350

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	0.74
DANN	Benign	0.66
PhyloP100		-0.62
Mutation Taster		=99/1	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: rs138794390; hg19: chr18-24496946; COSMIC: COSV52437276;