8-69672971-C-G

Position:

• chr8-69672971-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_030958.3(SLCO5A1):​c.2445G>C​(p.Gln815His) 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: 32)
• Consequence: SLCO5A1 NM_030958.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -3.56

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.048036575).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLCO5A1	NM_030958.3	c.2445G>C	p.Gln815His	missense_variant	10/10	ENST00000260126.9	NP_112220.2
SLCO5A1	NM_001146009.1	c.2280G>C	p.Gln760His	missense_variant	8/8		NP_001139481.1
SLCO5A1	NM_001146008.2	c.*316G>C		3_prime_UTR_variant	8/8		NP_001139480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLCO5A1	ENST00000260126.9	c.2445G>C	p.Gln815His	missense_variant	10/10	1	NM_030958.3	ENSP00000260126.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jul 07, 2023

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 output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 2049883). This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 815 of the SLCO5A1 protein (p.Gln815His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SLCO5A1-related conditions. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.0010
DANN	Benign	0.64
DEOGEN2	Benign	0.0017	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.021	N
LIST_S2	Benign	0.54	T;T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.048	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.55	N;.
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.54	N;N
REVEL	Benign	0.060
Sift	Benign	0.39	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.0	B;.
Vest4		0.029
MutPred		0.16		Gain of sheet (P = 0.0344);.;
MVP		0.40
MPC		0.27
ClinPred		0.049	T
GERP RS		-11
Varity_R		0.034
gMVP		0.40

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: rs1813388849; hg19: chr8-70585206;