8-69672888-G-A

Variant summary

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

The NM_030958.3(SLCO5A1):c.2528C>T(p.Ala843Val) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLCO5A1 NM_030958.3 missense
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: 3.34

Genes affected

SLCO5A1 (HGNC:19046): (solute carrier organic anion transporter family member 5A1) Predicted to enable sodium-independent organic anion transmembrane transporter activity. Predicted to be involved in sodium-independent organic anion transport. Located in intracellular membrane-bounded organelle and 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=0.13974047).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO5A1	NM_030958.3	c.2528C>T	p.Ala843Val	missense_variant	10/10	ENST00000260126.9
SLCO5A1	NM_001146009.1	c.2363C>T	p.Ala788Val	missense_variant	8/8
SLCO5A1	NM_001146008.2	c.*399C>T		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO5A1	ENST00000260126.9	c.2528C>T	p.Ala843Val	missense_variant	10/10	1	NM_030958.3	P1
SLCO5A1	ENST00000530307.1	c.2363C>T	p.Ala788Val	missense_variant	8/8	1
SLCO5A1	ENST00000524945.5	c.*399C>T		3_prime_UTR_variant	8/8	2
SLCO5A1	ENST00000526750.1	c.*874C>T		3_prime_UTR_variant, NMD_transcript_variant	6/6	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 23, 2023

The c.2528C>T (p.A843V) alteration is located in exon 10 (coding exon 9) of the SLCO5A1 gene. This alteration results from a C to T substitution at nucleotide position 2528, causing the alanine (A) at amino acid position 843 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Oct 17, 2022

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with SLCO5A1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 843 of the SLCO5A1 protein (p.Ala843Val). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
Cadd	Benign	15
Dann	Benign	0.97
DEOGEN2	Benign	0.0045	T;.
Eigen	Benign	-0.54
Eigen_PC	Benign	-0.52
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.62	T;T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.14	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.073
Sift	Uncertain	0.010	D;D
Sift4G	Benign	0.21	T;T
Polyphen		0.22	B;.
Vest4		0.13
MutPred		0.14		Loss of relative solvent accessibility (P = 0.0676);.;
MVP		0.57
MPC		0.31
ClinPred		0.36	T
GERP RS		3.6
Varity_R		0.057
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr8-70585123;