Genetic Variant SLC22A8:p.Thr241Thr (chr11-62998959-A-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004254.4(SLC22A8):c.723T>A(p.Thr241Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,613,400 control chromosomes in the GnomAD database, including 25,912 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.15 ( 2219 hom., cov: 33)

Exomes 𝑓: 0.17 ( 23693 hom. )

Consequence

SLC22A8
NM_004254.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.53

Publications

29 publications found

Variant links:

Genes affected

SLC22A8 (HGNC:10972): (solute carrier family 22 member 8) This gene encodes a protein involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, May 2010]

SLC22A8 links:

ENSG00000301851 (HGNC:):

ENSG00000301851 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP7

Synonymous conserved (PhyloP=-4.53 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A8	NM_004254.4 link	c.723T>A	p.Thr241Thr	synonymous_variant	Exon 5 of 11	ENST00000336232.7	NP_004245.2	Q8TCC7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A8	ENST00000336232.7 link	c.723T>A	p.Thr241Thr	synonymous_variant	Exon 5 of 11	1	NM_004254.4	ENSP00000337335.2		Q8TCC7-1

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23467

AN:

152164

Hom.:

2214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0624

Gnomad AMI

AF:

0.0903

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.196

Gnomad FIN

AF:

0.136

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.166

Gnomad OTH

AF:

0.177

GnomAD2 exomes

AF:

0.193

AC:

48385

AN:

251080

AF XY:

0.190

show subpopulations

Gnomad AFR exome

AF:

0.0609

Gnomad AMR exome

AF:

0.344

Gnomad ASJ exome

AF:

0.220

Gnomad EAS exome

AF:

0.244

Gnomad FIN exome

AF:

0.136

Gnomad NFE exome

AF:

0.162

Gnomad OTH exome

AF:

0.197

GnomAD4 exome

AF:

0.174

AC:

253864

AN:

1461118

Hom.:

23693

Cov.:

AF XY:

0.175

AC XY:

126861

AN XY:

726754

show subpopulations

African (AFR)

AF:

0.0538

AC:

1800

AN:

33480

American (AMR)

AF:

0.347

AC:

15490

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.222

AC:

5788

AN:

26124

East Asian (EAS)

AF:

0.266

AC:

10544

AN:

39676

South Asian (SAS)

AF:

0.211

AC:

18175

AN:

86204

European-Finnish (FIN)

AF:

0.134

AC:

7167

AN:

53408

Middle Eastern (MID)

AF:

0.175

AC:

1012

AN:

5768

European-Non Finnish (NFE)

AF:

0.165

AC:

182977

AN:

1111384

Other (OTH)

AF:

0.181

AC:

10911

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

10661

21321

31982

42642

53303

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6632

13264

19896

26528

33160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.154

AC:

23481

AN:

152282

Hom.:

2219

Cov.:

AF XY:

0.157

AC XY:

11707

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0622

AC:

2585

AN:

41578

American (AMR)

AF:

0.300

AC:

4589

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

756

AN:

3470

East Asian (EAS)

AF:

0.261

AC:

1354

AN:

5184

South Asian (SAS)

AF:

0.197

AC:

953

AN:

4828

European-Finnish (FIN)

AF:

0.136

AC:

1439

AN:

10612

Middle Eastern (MID)

AF:

0.150

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.166

AC:

11307

AN:

68016

Other (OTH)

AF:

0.176

AC:

372

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1027

2054

3080

4107

5134

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

266

532

798

1064

1330

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.160

Hom.:

1606

Bravo

AF:

0.163

Asia WGS

AF:

0.206

AC:

716

AN:

3478

EpiCase

AF:

0.164

EpiControl

AF:

0.168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.57

(source)

DANN

Benign

0.48

PhyloP100

-4.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over