Genetic Variant NM_173488.5:c.2053A>G (chr5-102373459-T-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_173488.5(SLCO6A1):c.2053A>G(p.Thr685Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,413,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SLCO6A1
NM_173488.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.17

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: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.038386583).

BP6

Variant 5-102373459-T-C is Benign according to our data. Variant chr5-102373459-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3320407.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.2053A>G	p.Thr685Ala	missense	Exon 13 of 14	NP_775759.3
SLCO6A1	NM_001289002.2		c.2053A>G	p.Thr685Ala	missense	Exon 13 of 14	NP_001275931.1	Q86UG4-1
SLCO6A1	NM_001289004.2		c.1867A>G	p.Thr623Ala	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.2053A>G	p.Thr685Ala	missense	Exon 13 of 14	ENSP00000421339.1	Q86UG4-1
SLCO6A1	ENST00000379807.7	TSL:1	c.2053A>G	p.Thr685Ala	missense	Exon 13 of 14	ENSP00000369135.3	Q86UG4-1
SLCO6A1	ENST00000389019.7	TSL:1	c.1867A>G	p.Thr623Ala	missense	Exon 12 of 13	ENSP00000373671.3	Q86UG4-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000106

AC:

AN:

1413622

Hom.:

Cov.:

AF XY:

0.0000128

AC XY:

AN XY:

702344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31748

American (AMR)

AF:

0.00

AC:

AN:

38262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25050

East Asian (EAS)

AF:

0.00

AC:

AN:

37596

South Asian (SAS)

AF:

0.00

AC:

AN:

76418

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50948

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5516

European-Non Finnish (NFE)

AF:

0.0000138

AC:

AN:

1089926

Other (OTH)

AF:

0.00

AC:

AN:

58158

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.438

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.:

ClinVar

ClinVar submissions

Significance:Likely benign

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

Benign

0.060

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.0050

(source)

DANN

Benign

0.11

DEOGEN2

Benign

0.048

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0019

LIST_S2

Benign

0.43

M_CAP

Benign

0.0017

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.20

PhyloP100

-2.2

PrimateAI

Benign

0.29

PROVEAN

Benign

0.46

REVEL

Benign

0.015

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0030

Vest4

0.049

MutPred

0.44

Loss of glycosylation at T685 (P = 0.2333)

MVP

0.055

MPC

0.11

ClinPred

0.054

GERP RS

-1.1

PromoterAI

0.023

Neutral

(source)

Varity_R

0.020

gMVP

0.065

Mutation Taster

=95/5

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