5-102373384-T-A

Variant names:

• chr5-102373384-T-A
• rs76193868
• NM_173488.5:c.2128A>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_173488.5(SLCO6A1):​c.2128A>T​(p.Lys710*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000351 in 1,423,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000035 (0 hom.)
• Consequence: SLCO6A1 NM_173488.5 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173488.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO6A1	NM_173488.5	MANE Select	c.2128A>T	p.Lys710*	stop_gained	Exon 13 of 14	NP_775759.3
	SLCO6A1	NM_001289002.2		c.2128A>T	p.Lys710*	stop_gained	Exon 13 of 14	NP_001275931.1	Q86UG4-1
	SLCO6A1	NM_001289004.2		c.1942A>T	p.Lys648*	stop_gained	Exon 12 of 13	NP_001275933.1	Q86UG4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLCO6A1	ENST00000506729.6	TSL:1 MANE Select	c.2128A>T	p.Lys710*	stop_gained	Exon 13 of 14	ENSP00000421339.1	Q86UG4-1
	SLCO6A1	ENST00000379807.7	TSL:1	c.2128A>T	p.Lys710*	stop_gained	Exon 13 of 14	ENSP00000369135.3	Q86UG4-1
	SLCO6A1	ENST00000389019.7	TSL:1	c.1942A>T	p.Lys648*	stop_gained	Exon 12 of 13	ENSP00000373671.3	Q86UG4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000351 AC: 5 AN: 1423048 Hom.: 0 Cov.: 30 AF XY: 0.00000566 AC XY: 4 AN XY: 707100

African (AFR) AF: 0.00 AC: 0 AN: 31890

American (AMR) AF: 0.00 AC: 0 AN: 37722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25348

East Asian (EAS) AF: 0.00 AC: 0 AN: 37900

South Asian (SAS) AF: 0.00 AC: 0 AN: 77050

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52082

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5624

European-Non Finnish (NFE) AF: 0.00000456 AC: 5 AN: 1096856

Other (OTH) AF: 0.00 AC: 0 AN: 58576

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.31	D
BayesDel_noAF	Pathogenic	0.21
CADD	Pathogenic	33
DANN	Benign	0.95
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.018	N
PhyloP100		0.096
Vest4		0.096
GERP RS		-0.61
PromoterAI		-0.038	Neutral
Mutation Taster		=125/75	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs76193868; hg19: chr5-101709088;