5-102373370-T-G

Variant names:

• chr5-102373370-T-G
• rs146381310
• NM_173488.5:c.2142A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_173488.5(SLCO6A1):​c.2142A>C​(p.Lys714Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000708 in 1,412,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. K714K) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: SLCO6A1 NM_173488.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.66
• Publications: 1 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.055285126).

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.2142A>C	p.Lys714Asn	missense	Exon 13 of 14	NP_775759.3
	SLCO6A1	NM_001289002.2		c.2142A>C	p.Lys714Asn	missense	Exon 13 of 14	NP_001275931.1	Q86UG4-1
	SLCO6A1	NM_001289004.2		c.1956A>C	p.Lys652Asn	missense	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.2142A>C	p.Lys714Asn	missense	Exon 13 of 14	ENSP00000421339.1	Q86UG4-1
	SLCO6A1	ENST00000379807.7	TSL:1	c.2142A>C	p.Lys714Asn	missense	Exon 13 of 14	ENSP00000369135.3	Q86UG4-1
	SLCO6A1	ENST00000389019.7	TSL:1	c.1956A>C	p.Lys652Asn	missense	Exon 12 of 13	ENSP00000373671.3	Q86UG4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000450 AC: 1 AN: 222038 AF XY: 0.00000827

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000189

GnomAD4 exome AF: 7.08e-7 AC: 1 AN: 1412224 Hom.: 0 Cov.: 30 AF XY: 0.00000143 AC XY: 1 AN XY: 701236

African (AFR) AF: 0.00 AC: 0 AN: 31428

American (AMR) AF: 0.00 AC: 0 AN: 36498

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25114

East Asian (EAS) AF: 0.00 AC: 0 AN: 37352

South Asian (SAS) AF: 0.0000134 AC: 1 AN: 74548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51636

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5562

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092054

Other (OTH) AF: 0.00 AC: 0 AN: 58032

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.80
DANN	Benign	0.50
DEOGEN2	Benign	0.087	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0090	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N
PhyloP100		-1.7
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.011
Sift	Benign	0.30	T
Sift4G	Benign	0.18	T
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.29		Loss of methylation at K714 (P = 0.03)
MVP		0.061
MPC		0.13
ClinPred		0.036	T
GERP RS		-6.7
PromoterAI		0.0090	Neutral
Varity_R		0.044
gMVP		0.18
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs146381310; hg19: chr5-101709074;