1-205918943-T-C

Position:

• chr1-205918943-T-C

Variant summary

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

The NM_052934.4(SLC26A9):​c.2153A>G​(p.Asp718Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC26A9 NM_052934.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A9	NM_052934.4	c.2153A>G	p.Asp718Gly	missense_variant	19/21	ENST00000367135.8	NP_443166.1
SLC26A9	NM_134325.3	c.2153A>G	p.Asp718Gly	missense_variant	19/22		NP_599152.2
SLC26A9	XM_011509121.3	c.1886A>G	p.Asp629Gly	missense_variant	18/20		XP_011507423.1
SLC26A9	XM_011509122.3	c.1661A>G	p.Asp554Gly	missense_variant	16/18		XP_011507424.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A9	ENST00000367135.8	c.2153A>G	p.Asp718Gly	missense_variant	19/21	1	NM_052934.4	ENSP00000356103	P1
SLC26A9	ENST00000340781.8	c.2153A>G	p.Asp718Gly	missense_variant	18/21	1		ENSP00000341682
SLC26A9	ENST00000367134.2	c.2153A>G	p.Asp718Gly	missense_variant	19/22	5		ENSP00000356102
SLC26A9	ENST00000491127.5	n.1537A>G		non_coding_transcript_exon_variant	11/13	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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 08, 2023

The c.2153A>G (p.D718G) alteration is located in exon 19 (coding exon 18) of the SLC26A9 gene. This alteration results from a A to G substitution at nucleotide position 2153, causing the aspartic acid (D) at amino acid position 718 to be replaced by a glycine (G). 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	Uncertain	0.10	D
BayesDel_noAF	Benign	-0.090
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.52	.;D;.
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.82	.;T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.22	T;T;T
MetaSVM	Benign	-0.55	T
MutationAssessor	Benign	1.4	L;L;L
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Benign	0.46	T
PROVEAN	Uncertain	-3.4	D;D;D
REVEL	Benign	0.23
Sift	Uncertain	0.0050	D;D;D
Sift4G	Uncertain	0.013	D;D;D
Polyphen		0.32	.;B;.
Vest4		0.21
MutPred		0.40		Loss of stability (P = 0.1322);Loss of stability (P = 0.1322);Loss of stability (P = 0.1322);
MVP		0.46
MPC		0.26
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.66
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.39		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.39		Position offset: 42

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: chr1-205888071;