rs9438438

Variant names:

• chr1-205914934-T-C
• rs9438438
• ENST00000340781.8:c.2622A>G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_134325.3(SLC26A9):​c.2622A>G​(p.Pro874Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0841 in 1,614,076 control chromosomes in the GnomAD database, including 6,264 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (894 hom., cov: 32)
  • Exomes 𝑓: 0.082 (5370 hom.)
• Consequence: SLC26A9 NM_134325.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0320
• Publications: 7 publications found

Genes affected

SLC26A9 (HGNC:14469): (solute carrier family 26 member 9) This gene is one member of a family of sulfate/anion transporter genes. Family members are well conserved in their genomic (number and size of exons) and protein (aa length among species) structures yet have markedly different tissue expression patterns. The product of this gene is a highly selective chloride ion channel regulated by WNK kinases. Alternative splicing results in multiple transcript variants encoding differing isoforms.[provided by RefSeq, Dec 2008]

SLC26A9 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-205914934-T-C is Benign according to our data. Variant chr1-205914934-T-C is described in ClinVar as Benign. ClinVar VariationId is 403450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.032 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134325.3. 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
	SLC26A9	NM_052934.4	MANE Select	c.*423A>G		3_prime_UTR	Exon 21 of 21	NP_443166.1	Q7LBE3-1
	SLC26A9	NM_134325.3		c.2622A>G	p.Pro874Pro	synonymous	Exon 22 of 22	NP_599152.2	Q7LBE3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC26A9	ENST00000340781.8	TSL:1	c.2622A>G	p.Pro874Pro	synonymous	Exon 21 of 21	ENSP00000341682.4	Q7LBE3-2
	SLC26A9	ENST00000367135.8	TSL:1 MANE Select	c.*423A>G		3_prime_UTR	Exon 21 of 21	ENSP00000356103.3	Q7LBE3-1
	SLC26A9	ENST00000367134.2	TSL:5	c.2622A>G	p.Pro874Pro	synonymous	Exon 22 of 22	ENSP00000356102.2	Q7LBE3-2

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15336 AN: 152138 Hom.: 890 Cov.: 32

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.130

Gnomad AMR AF: 0.0753

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0259

Gnomad FIN AF: 0.0623

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0886

Gnomad OTH AF: 0.102

GnomAD2 exomes AF: 0.0742 AC: 18631 AN: 251188 AF XY: 0.0724

Gnomad AFR exome AF: 0.163

Gnomad AMR exome AF: 0.0523

Gnomad ASJ exome AF: 0.108

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0623

Gnomad NFE exome AF: 0.0902

Gnomad OTH exome AF: 0.0860

GnomAD4 exome AF: 0.0824 AC: 120443 AN: 1461820 Hom.: 5370 Cov.: 32 AF XY: 0.0811 AC XY: 58985 AN XY: 727220

African (AFR) AF: 0.168 AC: 5618 AN: 33480

American (AMR) AF: 0.0543 AC: 2426 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.108 AC: 2825 AN: 26128

East Asian (EAS) AF: 0.000101 AC: 4 AN: 39700

South Asian (SAS) AF: 0.0307 AC: 2652 AN: 86248

European-Finnish (FIN) AF: 0.0640 AC: 3418 AN: 53420

Middle Eastern (MID) AF: 0.116 AC: 671 AN: 5766

European-Non Finnish (NFE) AF: 0.0882 AC: 98062 AN: 1111974

Other (OTH) AF: 0.0789 AC: 4767 AN: 60394

GnomAD4 genome AF: 0.101 AC: 15353 AN: 152256 Hom.: 894 Cov.: 32 AF XY: 0.0965 AC XY: 7182 AN XY: 74438

African (AFR) AF: 0.160 AC: 6632 AN: 41500

American (AMR) AF: 0.0752 AC: 1151 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 397 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.0259 AC: 125 AN: 4822

European-Finnish (FIN) AF: 0.0623 AC: 662 AN: 10618

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0886 AC: 6025 AN: 68034

Other (OTH) AF: 0.101 AC: 214 AN: 2114

Alfa AF: 0.0958 Hom.: 1108

Bravo AF: 0.106

EpiCase AF: 0.0965

EpiControl AF: 0.0978

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.8
DANN	Benign	0.42
PhyloP100		0.032
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: rs9438438; hg19: chr1-205884062; COSMIC: COSV108162889;