8-69672979-C-CT

Variant summary

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

The NM_030958.3(SLCO5A1):c.2436_2437insA(p.Gly813ArgfsTer45) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLCO5A1 NM_030958.3 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0680

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO5A1	NM_030958.3	c.2436_2437insA	p.Gly813ArgfsTer45	frameshift_variant	10/10	ENST00000260126.9
SLCO5A1	NM_001146009.1	c.2271_2272insA	p.Gly758ArgfsTer45	frameshift_variant	8/8
SLCO5A1	NM_001146008.2	c.*307_*308insA		3_prime_UTR_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO5A1	ENST00000260126.9	c.2436_2437insA	p.Gly813ArgfsTer45	frameshift_variant	10/10	1	NM_030958.3	P1
SLCO5A1	ENST00000530307.1	c.2271_2272insA	p.Gly758ArgfsTer45	frameshift_variant	8/8	1
SLCO5A1	ENST00000524945.5	c.*307_*308insA		3_prime_UTR_variant	8/8	2
SLCO5A1	ENST00000526750.1	c.*782_*783insA		3_prime_UTR_variant, NMD_transcript_variant	6/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Invitae

Dec 03, 2021

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 results in a frameshift in the SLCO5A1 gene (p.Gly813Argfs*45). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 36 amino acid(s) of the SLCO5A1 protein and extend the protein by 8 additional amino acid residues. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -

Computational scores

Source: dbNSFP v4.3

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: chr8-70585214;