Genetic Variant NM_173488.5:c.1592G>C (chr5-102413024-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_173488.5(SLCO6A1):c.1592G>C(p.Gly531Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000719 in 1,391,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

SLCO6A1
NM_173488.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.25

Publications

0 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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.932

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.1592G>C	p.Gly531Ala	missense	Exon 9 of 14	NP_775759.3
SLCO6A1	NM_001289002.2		c.1592G>C	p.Gly531Ala	missense	Exon 9 of 14	NP_001275931.1	Q86UG4-1
SLCO6A1	NM_001289004.2		c.1406G>C	p.Gly469Ala	missense	Exon 8 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.1592G>C	p.Gly531Ala	missense	Exon 9 of 14	ENSP00000421339.1	Q86UG4-1
SLCO6A1	ENST00000379807.7	TSL:1	c.1592G>C	p.Gly531Ala	missense	Exon 9 of 14	ENSP00000369135.3	Q86UG4-1
SLCO6A1	ENST00000389019.7	TSL:1	c.1406G>C	p.Gly469Ala	missense	Exon 8 of 13	ENSP00000373671.3	Q86UG4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.19e-7

AC:

AN:

1391144

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

688898

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29712

American (AMR)

AF:

0.00

AC:

AN:

32534

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24812

East Asian (EAS)

AF:

0.00

AC:

AN:

35836

South Asian (SAS)

AF:

0.00

AC:

AN:

69206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4274

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1084682

Other (OTH)

AF:

0.0000174

AC:

AN:

57488

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.775

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.74

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Pathogenic

0.75

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.84

M_CAP

Benign

0.0063

MetaRNN

Pathogenic

0.93

MetaSVM

Benign

-0.84

MutationAssessor

Pathogenic

3.8

PhyloP100

3.2

PrimateAI

Benign

0.46

PROVEAN

Pathogenic

-5.5

REVEL

Benign

0.21

Sift

Pathogenic

0.0

Sift4G

Benign

0.063

Polyphen

1.0

Vest4

0.64

MutPred

0.84

Gain of catalytic residue at G531 (P = 0.164)

MVP

0.33

MPC

0.55

ClinPred

0.99

GERP RS

4.3

Varity_R

0.91

gMVP

0.84

Mutation Taster

=66/34

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over