5-102373447-A-C

Position:

• chr5-102373447-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173488.5(SLCO6A1):​c.2065T>G​(p.Phe689Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLCO6A1 NM_173488.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.50

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.070139885).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO6A1	NM_173488.5	c.2065T>G	p.Phe689Val	missense_variant	13/14	ENST00000506729.6	NP_775759.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO6A1	ENST00000506729.6	c.2065T>G	p.Phe689Val	missense_variant	13/14	1	NM_173488.5	ENSP00000421339.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 10, 2024

The c.2065T>G (p.F689V) alteration is located in exon 13 (coding exon 13) of the SLCO6A1 gene. This alteration results from a T to G substitution at nucleotide position 2065, causing the phenylalanine (F) at amino acid position 689 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	0.0030
DANN	Benign	0.41
DEOGEN2	Benign	0.29	T;T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.8
FATHMM_MKL	Benign	0.0024	N
LIST_S2	Benign	0.40	.;T;T;T
M_CAP	Benign	0.0047	T
MetaRNN	Benign	0.070	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N;.;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-2.3	N;N;N;N
REVEL	Benign	0.032
Sift	Benign	0.52	T;T;T;T
Sift4G	Benign	0.46	T;T;T;T
Polyphen		0.31	B;B;B;P
Vest4		0.091
MutPred		0.43		Loss of ubiquitination at K692 (P = 0.1881);Loss of ubiquitination at K692 (P = 0.1881);.;.;
MVP		0.076
MPC		0.15
ClinPred		0.34	T
GERP RS		-6.7
Varity_R		0.040
gMVP		0.13

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

LitVar

Other links and lift over

dbSNP: rs1750739217; hg19: chr5-101709151;