dbSNP rs138607526: SLC16A9:p.Phe501Val (chr10-59652801-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_194298.3(SLC16A9):c.1501T>G(p.Phe501Val) variant causes a missense change. The variant allele was found at a frequency of 0.0131 in 1,611,346 control chromosomes in the GnomAD database, including 185 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 6 hom., cov: 32)

Exomes 𝑓: 0.014 ( 179 hom. )

Consequence

SLC16A9
NM_194298.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.03

Publications

7 publications found

Variant links:

Genes affected

SLC16A9 (HGNC:23520): (solute carrier family 16 member 9) Predicted to enable monocarboxylic acid transmembrane transporter activity. Involved in urate metabolic process. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC16A9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003896594).

BP6

Variant 10-59652801-A-C is Benign according to our data. Variant chr10-59652801-A-C is described in ClinVar as [Benign]. Clinvar id is 774470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.0137 (19946/1459096) while in subpopulation NFE AF = 0.0167 (18595/1111234). AF 95% confidence interval is 0.0165. There are 179 homozygotes in GnomAdExome4. There are 9586 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC16A9	NM_194298.3 link	c.1501T>G	p.Phe501Val	missense_variant	Exon 6 of 6	ENST00000395348.8	NP_919274.1	Q7RTY1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC16A9	ENST00000395348.8 link	c.1501T>G	p.Phe501Val	missense_variant	Exon 6 of 6	5	NM_194298.3	ENSP00000378757.3		Q7RTY1
SLC16A9	ENST00000395347.1 link	c.1501T>G	p.Phe501Val	missense_variant	Exon 6 of 6	2		ENSP00000378756.1		Q7RTY1

Frequencies

GnomAD3 genomes

AF:

0.00786

AC:

1195

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00237

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00413

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.00650

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0139

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00780

AC:

1935

AN:

248186

AF XY:

0.00799

show subpopulations

Gnomad AFR exome

AF:

0.00240

Gnomad AMR exome

AF:

0.00260

Gnomad ASJ exome

AF:

0.00332

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00824

Gnomad NFE exome

AF:

0.0138

Gnomad OTH exome

AF:

0.00708

GnomAD4 exome

AF:

0.0137

AC:

19946

AN:

1459096

Hom.:

179

Cov.:

AF XY:

0.0132

AC XY:

9586

AN XY:

725704

show subpopulations

African (AFR)

AF:

0.00192

AC:

AN:

33326

American (AMR)

AF:

0.00302

AC:

133

AN:

44008

Ashkenazi Jewish (ASJ)

AF:

0.00253

AC:

AN:

26048

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.000199

AC:

AN:

85364

European-Finnish (FIN)

AF:

0.00719

AC:

384

AN:

53404

Middle Eastern (MID)

AF:

0.000348

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0167

AC:

18595

AN:

1111234

Other (OTH)

AF:

0.0114

AC:

685

AN:

60296

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

931

1861

2792

3722

4653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00785

AC:

1195

AN:

152250

Hom.:

Cov.:

AF XY:

0.00720

AC XY:

536

AN XY:

74436

show subpopulations

African (AFR)

AF:

0.00236

AC:

AN:

41540

American (AMR)

AF:

0.00412

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00231

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.000621

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00650

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0139

AC:

944

AN:

68022

Other (OTH)

AF:

0.00379

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

134

202

269

336

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0123

Hom.:

Bravo

AF:

0.00781

TwinsUK

AF:

0.0178

AC:

ALSPAC

AF:

0.0145

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0137

AC:

118

ExAC

AF:

0.00736

AC:

893

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0141

EpiControl

AF:

0.0122

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Oct 13, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0050

T;T

Eigen

Benign

-0.28

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.77

.;T

MetaRNN

Benign

0.0039

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

N;N

PhyloP100

4.0

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.050

N;N

REVEL

Benign

0.11

Sift

Benign

0.16

T;T

Sift4G

Uncertain

0.016

D;D

Polyphen

0.081

B;B

Vest4

0.15

MVP

0.043

MPC

0.20

ClinPred

0.016

GERP RS

5.6

Varity_R

0.10

gMVP

0.52

Mutation Taster

=98/2

polymorphism

(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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rs138607526

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over