chr5-102399571-C-T

Variant names:

• chr5-102399571-C-T
• rs547449839
• NM_173488.5:c.1798G>A

Variant summary

Our verdict is Likely benign. The variant received -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. 16/22 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
• 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 -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 VariationId is 3165879.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1798G>A	p.Val600Ile	missense	Exon 10 of 14	NP_775759.3
	SLCO6A1	NM_001289002.2		c.1798G>A	p.Val600Ile	missense	Exon 10 of 14	NP_001275931.1	Q86UG4-1
	SLCO6A1	NM_001289004.2		c.1612G>A	p.Val538Ile	missense	Exon 9 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.1798G>A	p.Val600Ile	missense	Exon 10 of 14	ENSP00000421339.1	Q86UG4-1
	SLCO6A1	ENST00000379807.7	TSL:1	c.1798G>A	p.Val600Ile	missense	Exon 10 of 14	ENSP00000369135.3	Q86UG4-1
	SLCO6A1	ENST00000389019.7	TSL:1	c.1612G>A	p.Val538Ile	missense	Exon 9 of 13	ENSP00000373671.3	Q86UG4-2

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

GnomAD2 exomes AF: 0.00000826 AC: 2 AN: 242198 AF XY: 0.0000152

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 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

African (AFR) AF: 0.0000307 AC: 1 AN: 32542

American (AMR) AF: 0.00 AC: 0 AN: 41730

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24596

East Asian (EAS) AF: 0.00 AC: 0 AN: 39146

South Asian (SAS) AF: 0.00 AC: 0 AN: 75800

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5554

European-Non Finnish (NFE) AF: 0.0000728 AC: 79 AN: 1084714

Other (OTH) AF: 0.0000344 AC: 2 AN: 58132

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

African (AFR) AF: 0.0000241 AC: 1 AN: 41496

American (AMR) AF: 0.00 AC: 0 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10548

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67934

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000227

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0011	N
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.0026	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.4	N
PhyloP100		-0.068
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.039
Sift	Benign	0.68	T
Sift4G	Benign	0.80	T
Polyphen		0.0	B
Vest4		0.055
MutPred		0.55		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
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs547449839; hg19: chr5-101735275; COSMIC: COSV101134284;