chr1-205920226-C-G

Position:

• chr1-205920226-C-G

Variant summary

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

The NM_052934.4(SLC26A9):​c.2060G>C​(p.Ser687Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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)
• Consequence: SLC26A9 NM_052934.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.09

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]

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=0.25961652).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A9	NM_052934.4	c.2060G>C	p.Ser687Thr	missense_variant	18/21	ENST00000367135.8	NP_443166.1
SLC26A9	NM_134325.3	c.2060G>C	p.Ser687Thr	missense_variant	18/22		NP_599152.2
SLC26A9	XM_011509121.3	c.1793G>C	p.Ser598Thr	missense_variant	17/20		XP_011507423.1
SLC26A9	XM_011509122.3	c.1568G>C	p.Ser523Thr	missense_variant	15/18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A9	ENST00000367135.8	c.2060G>C	p.Ser687Thr	missense_variant	18/21	1	NM_052934.4	ENSP00000356103	P1
SLC26A9	ENST00000340781.8	c.2060G>C	p.Ser687Thr	missense_variant	17/21	1		ENSP00000341682
SLC26A9	ENST00000367134.2	c.2060G>C	p.Ser687Thr	missense_variant	18/22	5		ENSP00000356102
SLC26A9	ENST00000491127.5	n.1444G>C		non_coding_transcript_exon_variant	10/13	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Dec 17, 2023

The c.2060G>C (p.S687T) alteration is located in exon 18 (coding exon 17) of the SLC26A9 gene. This alteration results from a G to C substitution at nucleotide position 2060, causing the serine (S) at amino acid position 687 to be replaced by a threonine (T). 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
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	0.0049	T
BayesDel_noAF	Benign	-0.23
CADD	Benign	22
DANN	Benign	0.94
DEOGEN2	Benign	0.13	.;T;.
Eigen	Benign	-0.0083
Eigen_PC	Benign	0.15
FATHMM_MKL	Benign	0.72	D
LIST_S2	Benign	0.79	.;T;T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Benign	-0.41	T
MutationAssessor	Uncertain	2.0	M;M;M
MutationTaster	Benign	0.97	N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	0.020	N;N;N
REVEL	Benign	0.28
Sift	Benign	0.31	T;T;T
Sift4G	Benign	0.59	T;T;T
Polyphen		0.081	.;B;.
Vest4		0.41
MutPred		0.51		Loss of ubiquitination at K685 (P = 0.0877);Loss of ubiquitination at K685 (P = 0.0877);Loss of ubiquitination at K685 (P = 0.0877);
MVP		0.55
MPC		0.23
ClinPred		0.39	T
GERP RS		4.5
Varity_R		0.50
gMVP		0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-205889354;