Genetic Variant SLCO6A1:p.Val463Met (chr5-102419911-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_173488.5(SLCO6A1):c.1387G>A(p.Val463Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,456,050 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V463L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLCO6A1
NM_173488.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.88

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25184003).

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.1387G>A	p.Val463Met	missense	Exon 8 of 14	NP_775759.3
SLCO6A1	NM_001289002.2		c.1387G>A	p.Val463Met	missense	Exon 8 of 14	NP_001275931.1	Q86UG4-1
SLCO6A1	NM_001289004.2		c.1201G>A	p.Val401Met	missense	Exon 7 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.1387G>A	p.Val463Met	missense	Exon 8 of 14	ENSP00000421339.1	Q86UG4-1
SLCO6A1	ENST00000379807.7	TSL:1	c.1387G>A	p.Val463Met	missense	Exon 8 of 14	ENSP00000369135.3	Q86UG4-1
SLCO6A1	ENST00000389019.7	TSL:1	c.1201G>A	p.Val401Met	missense	Exon 7 of 13	ENSP00000373671.3	Q86UG4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1456050

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

724130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33144

American (AMR)

AF:

0.00

AC:

AN:

43346

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26062

East Asian (EAS)

AF:

0.00

AC:

AN:

39400

South Asian (SAS)

AF:

0.00

AC:

AN:

84578

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53402

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110164

Other (OTH)

AF:

0.0000166

AC:

AN:

60198

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.044

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.077

Eigen

Benign

-0.91

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0077

LIST_S2

Benign

0.74

M_CAP

Benign

0.010

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.3

PhyloP100

-2.9

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.6

REVEL

Benign

0.13

Sift

Benign

0.067

Sift4G

Benign

0.094

Polyphen

0.99

Vest4

0.28

MutPred

0.57

Loss of catalytic residue at V463 (P = 0.0168)

MVP

0.081

MPC

0.44

ClinPred

0.61

GERP RS

-7.3

Varity_R

0.057

gMVP

0.15

Mutation Taster

=97/3

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over