5-102399571-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_173488.5(SLCO6A1):c.1798G>A(p.Val600Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000537 in 1,565,530 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000058 (0 hom.)
• Consequence: SLCO6A1 NM_173488.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0680

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028348833).
• BP6: Variant 5-102399571-C-T is Benign according to our data. Variant chr5-102399571-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3165879.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO6A1	NM_173488.5	c.1798G>A	p.Val600Ile	missense_variant	10/14	ENST00000506729.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO6A1	ENST00000506729.6	c.1798G>A	p.Val600Ile	missense_variant	10/14	1	NM_173488.5	P1
SLCO6A1	ENST00000379807.7	c.1798G>A	p.Val600Ile	missense_variant	10/14	1		P1
SLCO6A1	ENST00000389019.7	c.1612G>A	p.Val538Ile	missense_variant	9/13	1
SLCO6A1	ENST00000513675.1	c.1039G>A	p.Val347Ile	missense_variant	5/9	2

Frequencies

GnomAD3 genomes AF: 0.0000132 AC: 2 AN: 151888 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000826 AC: 2 AN: 242198 Hom.: 0 AF XY: 0.0000152 AC XY: 2 AN XY: 131378

Gnomad AFR exome AF: 0.0000626

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000902

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000580 AC: 82 AN: 1413524 Hom.: 0 Cov.: 30 AF XY: 0.0000613 AC XY: 43 AN XY: 701546

Gnomad4 AFR exome AF: 0.0000307

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000728

Gnomad4 OTH exome AF: 0.0000344

GnomAD4 genome AF: 0.0000132 AC: 2 AN: 152006 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74284

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.00000824 AC: 1

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 03, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.0070
Dann	Benign	0.70
DEOGEN2	Benign	0.036	T;T;.;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0011	N
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.028	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.4	N;N;.;.
MutationTaster	Benign	1.0	N;N;N;N;N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.50	N;N;N;N
REVEL	Benign	0.039
Sift	Benign	0.68	T;T;T;T
Sift4G	Benign	0.80	T;T;T;T
Polyphen		0.0	B;B;B;B
Vest4		0.055
MutPred		0.55		Loss of catalytic residue at V600 (P = 0.0219);Loss of catalytic residue at V600 (P = 0.0219);.;.;
MVP		0.040
MPC		0.086
ClinPred		0.019	T
GERP RS		0.12
Varity_R		0.024
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs547449839; hg19: chr5-101735275; COSMIC: COSV101134284;