5-102459702-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.975A>G(p.Ala325=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00146 in 1,610,912 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0011 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (0 hom.)
• Consequence: SLCO6A1 NM_173488.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.439

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=-0.58).
• BP6: Variant 5-102459702-T-C is Benign according to our data. Variant chr5-102459702-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 790450.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.439 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLCO6A1	NM_173488.5	c.975A>G	p.Ala325=	synonymous_variant	5/14	ENST00000506729.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLCO6A1	ENST00000506729.6	c.975A>G	p.Ala325=	synonymous_variant	5/14	1	NM_173488.5	P1

Frequencies

GnomAD3 genomes AF: 0.00114 AC: 174 AN: 152000 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000290

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.000918

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00188

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.000871 AC: 216 AN: 247892 Hom.: 0 AF XY: 0.000888 AC XY: 119 AN XY: 133992

Gnomad AFR exome AF: 0.000187

Gnomad AMR exome AF: 0.000828

Gnomad ASJ exome AF: 0.000302

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00158

Gnomad OTH exome AF: 0.000664

GnomAD4 exome AF: 0.00150 AC: 2184 AN: 1458794 Hom.: 0 Cov.: 31 AF XY: 0.00140 AC XY: 1019 AN XY: 725642

Gnomad4 AFR exome AF: 0.000362

Gnomad4 AMR exome AF: 0.000791

Gnomad4 ASJ exome AF: 0.000461

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000350

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00185

Gnomad4 OTH exome AF: 0.000929

GnomAD4 genome AF: 0.00114 AC: 173 AN: 152118 Hom.: 1 Cov.: 32 AF XY: 0.000901 AC XY: 67 AN XY: 74362

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000917

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000946

Gnomad4 NFE AF: 0.00188

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.00134 Hom.: 0

Bravo AF: 0.00124

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Jul 11, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	2.6
Dann	Benign	0.31

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: rs144439446; hg19: chr5-101795406;