1-205915125-G-A

Position:

• chr1-205915125-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_134325.3(SLC26A9):​c.2431C>T​(p.Pro811Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: SLC26A9 NM_134325.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.949

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07953712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A9	NM_052934.4	c.*232C>T		3_prime_UTR_variant	21/21	ENST00000367135.8	NP_443166.1
SLC26A9	NM_134325.3	c.2431C>T	p.Pro811Ser	missense_variant	22/22		NP_599152.2
SLC26A9	XM_011509121.3	c.*232C>T		3_prime_UTR_variant	20/20		XP_011507423.1
SLC26A9	XM_011509122.3	c.*232C>T		3_prime_UTR_variant	18/18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A9	ENST00000340781.8	c.2431C>T	p.Pro811Ser	missense_variant	21/21	1		ENSP00000341682.4
SLC26A9	ENST00000367135	c.*232C>T		3_prime_UTR_variant	21/21	1	NM_052934.4	ENSP00000356103.3
SLC26A9	ENST00000367134.2	c.2431C>T	p.Pro811Ser	missense_variant	22/22	5		ENSP00000356102.2
SLC26A9	ENST00000491127.5	n.1992C>T		non_coding_transcript_exon_variant	13/13	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461494 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727004

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 16, 2022

The c.2431C>T (p.P811S) alteration is located in exon 22 (coding exon 21) of the SLC26A9 gene. This alteration results from a C to T substitution at nucleotide position 2431, causing the proline (P) at amino acid position 811 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.028	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	4.7
DANN	Benign	0.88
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.48	.;T
M_CAP	Uncertain	0.13	D
MetaRNN	Benign	0.080	T;T
MetaSVM	Uncertain	-0.15	T
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.050	N;N
REVEL	Benign	0.15
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.32	T;T
Vest4		0.033
MutPred		0.32		Gain of helix (P = 0.005);Gain of helix (P = 0.005);
MVP		0.20
MPC		0.14
ClinPred		0.67	D
GERP RS		0.85
gMVP		0.049

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

Publications

LitVar

Other links and lift over

dbSNP: rs764909473; hg19: chr1-205884253;