dbSNP rs76193868: SLCO6A1:p.Lys710Glu (chr5-102373384-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_173488.5(SLCO6A1):c.2128A>G(p.Lys710Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0002 in 1,575,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

SLCO6A1
NM_173488.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0960

Publications

1 publications found

Variant links:

Genes affected

SLCO6A1 (HGNC:23613): (solute carrier organic anion transporter family member 6A1) Predicted to enable sodium-independent organic anion transmembrane transporter activity. Predicted to be involved in sodium-independent organic anion transport. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLCO6A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008686483).

BP6

Variant 5-102373384-T-C is Benign according to our data. Variant chr5-102373384-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 713079.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173488.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLCO6A1	NM_173488.5	MANE Select	c.2128A>G	p.Lys710Glu	missense	Exon 13 of 14	NP_775759.3
SLCO6A1	NM_001289002.2		c.2128A>G	p.Lys710Glu	missense	Exon 13 of 14	NP_001275931.1	Q86UG4-1
SLCO6A1	NM_001289004.2		c.1942A>G	p.Lys648Glu	missense	Exon 12 of 13	NP_001275933.1	Q86UG4-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLCO6A1	ENST00000506729.6	TSL:1 MANE Select	c.2128A>G	p.Lys710Glu	missense	Exon 13 of 14	ENSP00000421339.1	Q86UG4-1
SLCO6A1	ENST00000379807.7	TSL:1	c.2128A>G	p.Lys710Glu	missense	Exon 13 of 14	ENSP00000369135.3	Q86UG4-1
SLCO6A1	ENST00000389019.7	TSL:1	c.1942A>G	p.Lys648Glu	missense	Exon 12 of 13	ENSP00000373671.3	Q86UG4-2

Frequencies

GnomAD3 genomes

AF:

0.000980

AC:

149

AN:

152000

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00348

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000959

GnomAD2 exomes

AF:

0.000307

AC:

AN:

227658

AF XY:

0.000226

show subpopulations

Gnomad AFR exome

AF:

0.00358

Gnomad AMR exome

AF:

0.000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000466

Gnomad OTH exome

AF:

0.000183

GnomAD4 exome

AF:

0.000117

AC:

166

AN:

1423048

Hom.:

Cov.:

AF XY:

0.000102

AC XY:

AN XY:

707100

show subpopulations

African (AFR)

AF:

0.00329

AC:

105

AN:

31890

American (AMR)

AF:

0.000345

AC:

AN:

37722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25348

East Asian (EAS)

AF:

0.00

AC:

AN:

37900

South Asian (SAS)

AF:

0.00

AC:

AN:

77050

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52082

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5624

European-Non Finnish (NFE)

AF:

0.0000191

AC:

AN:

1096856

Other (OTH)

AF:

0.000444

AC:

AN:

58576

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000980

AC:

149

AN:

152118

Hom.:

Cov.:

AF XY:

0.000928

AC XY:

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.00347

AC:

144

AN:

41558

American (AMR)

AF:

0.000196

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67910

Other (OTH)

AF:

0.000949

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000271

Hom.:

Bravo

AF:

0.00119

ESP6500AA

AF:

0.00477

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000420

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.094

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.40

M_CAP

Benign

0.0057

MetaRNN

Benign

0.0087

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.69

PhyloP100

0.096

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.1

REVEL

Benign

0.18

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.011

Polyphen

0.94

Vest4

0.20

MVP

0.18

MPC

0.15

ClinPred

0.022

GERP RS

-0.61

PromoterAI

0.031

Neutral

(source)

Varity_R

0.11

gMVP

0.12

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over