rs34309781

Variant names:

• chr1-205915098-C-A
• rs34309781
• ENST00000340781.8:c.2458G>T

Your query was ambiguous. Multiple possible variants found:

• chr1-205915098-C-A
• chr1-205915098-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134325.3(SLC26A9):​c.2458G>T​(p.Ala820Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0161 in 1,613,942 control chromosomes in the GnomAD database, including 441 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A820T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.016 (61 hom., cov: 32)
  • Exomes 𝑓: 0.016 (380 hom.)
• Consequence: SLC26A9 NM_134325.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.24
• Publications: 5 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0018024445).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0633 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.*259G>T		3_prime_UTR	Exon 21 of 21	NP_443166.1	Q7LBE3-1
	SLC26A9	NM_134325.3		c.2458G>T	p.Ala820Ser	missense	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.2458G>T	p.Ala820Ser	missense	Exon 21 of 21	ENSP00000341682.4	Q7LBE3-2
	SLC26A9	ENST00000367135.8	TSL:1 MANE Select	c.*259G>T		3_prime_UTR	Exon 21 of 21	ENSP00000356103.3	Q7LBE3-1
	SLC26A9	ENST00000367134.2	TSL:5	c.2458G>T	p.Ala820Ser	missense	Exon 22 of 22	ENSP00000356102.2	Q7LBE3-2

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2446 AN: 152154 Hom.: 61 Cov.: 32

Gnomad AFR AF: 0.00391

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0665

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00848

Gnomad FIN AF: 0.0171

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0144

Gnomad OTH AF: 0.0201

GnomAD2 exomes AF: 0.0233 AC: 5834 AN: 250714 AF XY: 0.0206

Gnomad AFR exome AF: 0.00326

Gnomad AMR exome AF: 0.0941

Gnomad ASJ exome AF: 0.00709

Gnomad EAS exome AF: 0.000109

Gnomad FIN exome AF: 0.0191

Gnomad NFE exome AF: 0.0143

Gnomad OTH exome AF: 0.0165

GnomAD4 exome AF: 0.0161 AC: 23590 AN: 1461670 Hom.: 380 Cov.: 32 AF XY: 0.0155 AC XY: 11301 AN XY: 727120

African (AFR) AF: 0.00344 AC: 115 AN: 33478

American (AMR) AF: 0.0901 AC: 4028 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00774 AC: 202 AN: 26108

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0109 AC: 936 AN: 86196

European-Finnish (FIN) AF: 0.0186 AC: 996 AN: 53408

Middle Eastern (MID) AF: 0.00780 AC: 45 AN: 5768

European-Non Finnish (NFE) AF: 0.0147 AC: 16370 AN: 1111906

Other (OTH) AF: 0.0149 AC: 897 AN: 60392

GnomAD4 genome AF: 0.0161 AC: 2449 AN: 152272 Hom.: 61 Cov.: 32 AF XY: 0.0164 AC XY: 1220 AN XY: 74442

African (AFR) AF: 0.00390 AC: 162 AN: 41554

American (AMR) AF: 0.0667 AC: 1019 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5186

South Asian (SAS) AF: 0.00849 AC: 41 AN: 4832

European-Finnish (FIN) AF: 0.0171 AC: 182 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0144 AC: 977 AN: 68012

Other (OTH) AF: 0.0199 AC: 42 AN: 2112

Alfa AF: 0.0117 Hom.: 15

Bravo AF: 0.0211

TwinsUK AF: 0.0116 AC: 43

ALSPAC AF: 0.0119 AC: 46

ESP6500AA AF: 0.00431 AC: 19

ESP6500EA AF: 0.0165 AC: 142

ExAC AF: 0.0204 AC: 2474

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.0126

EpiControl AF: 0.0132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	0.044
DANN	Benign	0.74
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0095	N
LIST_S2	Benign	0.32	T
MetaRNN	Benign	0.0018	T
MetaSVM	Benign	-0.56	T
PhyloP100		-3.2
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.010	N
REVEL	Benign	0.23
Sift	Benign	0.17	T
Sift4G	Benign	0.84	T
Vest4		0.0070
MPC		0.12
ClinPred		0.00089	T
GERP RS		-6.2
gMVP		0.021
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: rs34309781; hg19: chr1-205884226;