rs17707331

Positions:

• chr6-35992613-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_052961.4(SLC26A8):​c.689G>A​(p.Ser230Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,613,622 control chromosomes in the GnomAD database, including 12,785 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.10 (940 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11845 hom.)
• Consequence: SLC26A8 NM_052961.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.156

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]

LOC105375035 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0041314363).
• BP6: Variant 6-35992613-C-T is Benign according to our data. Variant chr6-35992613-C-T is described in ClinVar as [Benign]. Clinvar id is 1243863.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.13 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC26A8	NM_052961.4	c.689G>A	p.Ser230Asn	missense_variant	6/20	ENST00000490799.6	NP_443193.1
LOC105375035	XR_926747.3			downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC26A8	ENST00000490799.6	c.689G>A	p.Ser230Asn	missense_variant	6/20	1	NM_052961.4	ENSP00000417638	P1
SLC26A8	ENST00000394602.6	c.627+5125G>A		intron_variant		1		ENSP00000378100
SLC26A8	ENST00000355574.6	c.689G>A	p.Ser230Asn	missense_variant	6/20	2		ENSP00000347778	P1
SLC26A8	ENST00000486155.1	n.1044G>A		non_coding_transcript_exon_variant	6/13	2

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15932 AN: 152110 Hom.: 939 Cov.: 32

Gnomad AFR AF: 0.0438

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.238

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.107

Gnomad FIN AF: 0.129

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.128

GnomAD3 exomes AF: 0.120 AC: 29994 AN: 250822 Hom.: 2031 AF XY: 0.122 AC XY: 16487 AN XY: 135580

Gnomad AFR exome AF: 0.0390

Gnomad AMR exome AF: 0.115

Gnomad ASJ exome AF: 0.227

Gnomad EAS exome AF: 0.0552

Gnomad SAS exome AF: 0.113

Gnomad FIN exome AF: 0.131

Gnomad NFE exome AF: 0.132

Gnomad OTH exome AF: 0.131

GnomAD4 exome AF: 0.123 AC: 179702 AN: 1461394 Hom.: 11845 Cov.: 32 AF XY: 0.123 AC XY: 89614 AN XY: 726998

Gnomad4 AFR exome AF: 0.0385

Gnomad4 AMR exome AF: 0.119

Gnomad4 ASJ exome AF: 0.232

Gnomad4 EAS exome AF: 0.0484

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.126

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.105 AC: 15935 AN: 152228 Hom.: 940 Cov.: 32 AF XY: 0.105 AC XY: 7809 AN XY: 74430

Gnomad4 AFR AF: 0.0437

Gnomad4 AMR AF: 0.113

Gnomad4 ASJ AF: 0.238

Gnomad4 EAS AF: 0.0550

Gnomad4 SAS AF: 0.108

Gnomad4 FIN AF: 0.129

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.127

Alfa AF: 0.131 Hom.: 3066

Bravo AF: 0.102

TwinsUK AF: 0.130 AC: 481

ALSPAC AF: 0.121 AC: 467

ESP6500AA AF: 0.0427 AC: 188

ESP6500EA AF: 0.133 AC: 1143

ExAC AF: 0.118 AC: 14348

Asia WGS AF: 0.0770 AC: 267 AN: 3478

EpiCase AF: 0.141

EpiControl AF: 0.133

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	4.7
DANN	Benign	0.16
DEOGEN2	Benign	0.37	T;T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.062	N
LIST_S2	Benign	0.62	.;T
MetaRNN	Benign	0.0041	T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.89	L;L
MutationTaster	Benign	0.95	P;P;P
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.32	N;N
REVEL	Benign	0.18
Sift	Benign	0.27	T;T
Sift4G	Benign	0.28	T;T
Polyphen		0.031	B;B
Vest4		0.032
MPC		0.21
ClinPred		0.0043	T
GERP RS		3.3
Varity_R		0.073
gMVP		0.56

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: rs17707331; hg19: chr6-35960390; COSMIC: COSV62885323; COSMIC: COSV62885323;