dbSNP rs1436687606: SLC26A8:p.Lys889Arg (chr6-35944147-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052961.4(SLC26A8):c.2666A>G(p.Lys889Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC26A8
NM_052961.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.728

Variant links:

Genes affected

SLC26A8 (HGNC:14468): (solute carrier family 26 member 8) This gene encodes a member of the SLC26 gene family of anion transporters. Family members are well conserved in gene structure and protein length yet have markedly different tissue expression patterns. The expression of this gene appears to be restricted to spermatocytes. Alternatively spliced transcript variants that encode different isoforms have been described. [provided by RefSeq, Jul 2010]

SLC26A8 links:

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ACMG classification

Classification made for transcript

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=0.09868616).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC26A8	NM_052961.4 link	c.2666A>G	p.Lys889Arg	missense_variant	Exon 20 of 20	ENST00000490799.6	NP_443193.1	Q96RN1-1A0A024RCV0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC26A8	ENST00000490799.6 link	c.2666A>G	p.Lys889Arg	missense_variant	Exon 20 of 20	1	NM_052961.4	ENSP00000417638.1		Q96RN1-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727248

show subpopulations

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 21, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.2666A>G (p.K889R) alteration is located in exon 20 (coding exon 19) of the SLC26A8 gene. This alteration results from a A to G substitution at nucleotide position 2666, causing the lysine (K) at amino acid position 889 to be replaced by an arginine (R). 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

0.082

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.8

DANN

Benign

0.75

DEOGEN2

Benign

0.041

T;.;T

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.31

.;T;T

M_CAP

Benign

0.0076

MetaRNN

Benign

0.099

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;.;N

PrimateAI

Benign

0.37

PROVEAN

Benign

-0.41

N;N;N

REVEL

Benign

0.028

Sift

Uncertain

0.014

D;D;D

Sift4G

Benign

0.19

T;T;T

Polyphen

0.023

B;B;B

Vest4

0.097

MutPred

0.15

Loss of ubiquitination at K889 (P = 0.002);.;Loss of ubiquitination at K889 (P = 0.002);

MVP

0.29

MPC

0.17

ClinPred

0.053

GERP RS

2.9

Varity_R

0.041

gMVP

0.034

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over