5-102399669-C-A

Variant names:

• chr5-102399669-C-A
• rs138283674
• NM_173488.5:c.1700G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173488.5(SLCO6A1):​c.1700G>T​(p.Arg567Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,308 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. 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. R567T) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SLCO6A1 NM_173488.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81
• Publications: 2 publications found

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]

ACMG classification

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=0.069643795).

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO6A1	NM_173488.5	MANE Select	c.1700G>T	p.Arg567Ile	missense	Exon 10 of 14	NP_775759.3
	SLCO6A1	NM_001289002.2		c.1700G>T	p.Arg567Ile	missense	Exon 10 of 14	NP_001275931.1	Q86UG4-1
	SLCO6A1	NM_001289004.2		c.1514G>T	p.Arg505Ile	missense	Exon 9 of 13	NP_001275933.1	Q86UG4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO6A1	ENST00000506729.6	TSL:1 MANE Select	c.1700G>T	p.Arg567Ile	missense	Exon 10 of 14	ENSP00000421339.1	Q86UG4-1
	SLCO6A1	ENST00000379807.7	TSL:1	c.1700G>T	p.Arg567Ile	missense	Exon 10 of 14	ENSP00000369135.3	Q86UG4-1
	SLCO6A1	ENST00000389019.7	TSL:1	c.1514G>T	p.Arg505Ile	missense	Exon 9 of 13	ENSP00000373671.3	Q86UG4-2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457308 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724948

African (AFR) AF: 0.00 AC: 0 AN: 33416

American (AMR) AF: 0.00 AC: 0 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25980

East Asian (EAS) AF: 0.0000253 AC: 1 AN: 39554

South Asian (SAS) AF: 0.00 AC: 0 AN: 85540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53234

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5746

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109010

Other (OTH) AF: 0.00 AC: 0 AN: 60170

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.22
DANN	Benign	0.92
DEOGEN2	Benign	0.068	T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.0060	N
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.070	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.2	L
PhyloP100		-1.8
PrimateAI	Benign	0.25	T
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.085
Sift	Benign	0.20	T
Sift4G	Benign	0.24	T
Polyphen		0.18	B
Vest4		0.19
MutPred		0.53		Loss of ubiquitination at K570 (P = 0.0396)
MVP		0.072
MPC		0.23
ClinPred		0.13	T
GERP RS		-11
Varity_R		0.098
gMVP		0.43
Mutation Taster		=96/4	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs138283674; hg19: chr5-101735373;