5-102373370-T-C

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_173488.5(SLCO6A1):c.2142A>G(p.Lys714=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,564,338 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00089 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (1 hom.)
• Consequence: SLCO6A1 NM_173488.5 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.66

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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 5-102373370-T-C is Benign according to our data. Variant chr5-102373370-T-C is described in ClinVar as [Benign]. Clinvar id is 721376.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.66 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO6A1	NM_173488.5	c.2142A>G	p.Lys714=	synonymous_variant	13/14	ENST00000506729.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO6A1	ENST00000506729.6	c.2142A>G	p.Lys714=	synonymous_variant	13/14	1	NM_173488.5	P1

Frequencies

GnomAD3 genomes AF: 0.000895 AC: 136 AN: 152014 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000265

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00169

Gnomad OTH AF: 0.000479

GnomAD3 exomes AF: 0.000923 AC: 205 AN: 222038 Hom.: 0 AF XY: 0.00101 AC XY: 122 AN XY: 120850

Gnomad AFR exome AF: 0.000545

Gnomad AMR exome AF: 0.0000769

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000163

Gnomad FIN exome AF: 0.000285

Gnomad NFE exome AF: 0.00174

Gnomad OTH exome AF: 0.000378

GnomAD4 exome AF: 0.00121 AC: 1711 AN: 1412206 Hom.: 1 Cov.: 30 AF XY: 0.00126 AC XY: 885 AN XY: 701230

Gnomad4 AFR exome AF: 0.000159

Gnomad4 AMR exome AF: 0.000164

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000215

Gnomad4 FIN exome AF: 0.000310

Gnomad4 NFE exome AF: 0.00148

Gnomad4 OTH exome AF: 0.000810

GnomAD4 genome AF: 0.000894 AC: 136 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.000726 AC XY: 54 AN XY: 74384

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00169

Gnomad4 OTH AF: 0.000474

Alfa AF: 0.00136 Hom.: 0

Bravo AF: 0.000922

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.46
Dann	Benign	0.42

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: rs146381310; hg19: chr5-101709074; COSMIC: COSV65810473;