5-102459704-C-A

Variant summary

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

The NM_173488.5(SLCO6A1):c.973G>T(p.Ala325Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A325A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLCO6A1 NM_173488.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.919

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO6A1	NM_173488.5	c.973G>T	p.Ala325Ser	missense_variant	5/14	ENST00000506729.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO6A1	ENST00000506729.6	c.973G>T	p.Ala325Ser	missense_variant	5/14	1	NM_173488.5	P1

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 specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 16, 2022

The c.973G>T (p.A325S) alteration is located in exon 5 (coding exon 5) of the SLCO6A1 gene. This alteration results from a G to T substitution at nucleotide position 973, causing the alanine (A) at amino acid position 325 to be replaced by a serine (S). 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	0.13
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
Cadd	Benign	5.8
Dann	Uncertain	0.99
DEOGEN2	Benign	0.069	T;T;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.39
FATHMM_MKL	Benign	0.037	N
M_CAP	Benign	0.063	D
MetaRNN	Uncertain	0.62	D;D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.2	M;M;.
MutationTaster	Benign	1.0	D;D;N;N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Uncertain	0.41
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.26	T;T;T
Polyphen		0.92	P;P;P
Vest4		0.31
MutPred		0.73		Loss of catalytic residue at A325 (P = 0.1799);Loss of catalytic residue at A325 (P = 0.1799);.;
MVP		0.61
MPC		0.28
ClinPred		0.83	D
GERP RS		2.6
Varity_R		0.16
gMVP		0.089

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: chr5-101795408;