NM_153276.3:c.149G>A

Variant names:

• chr11-62984542-C-T
• rs11568626
• NM_153276.3:c.149G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153276.3(SLC22A6):​c.149G>A​(p.Arg50His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 1,613,590 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.019 (84 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (78 hom.)
• Consequence: SLC22A6 NM_153276.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.978
• Publications: 35 publications found

Genes affected

SLC22A6 (HGNC:10970): (solute carrier family 22 member 6) The protein encoded by this gene is involved in the sodium-dependent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and may be localized to the basolateral membrane. Four transcript variants encoding four different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

ENSG00000301851 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0030465722).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0624 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153276.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A6	NM_153276.3	MANE Select	c.149G>A	p.Arg50His	missense	Exon 1 of 10	NP_695008.1
	SLC22A6	NM_004790.5		c.149G>A	p.Arg50His	missense	Exon 1 of 10	NP_004781.2
	SLC22A6	NM_153278.3		c.149G>A	p.Arg50His	missense	Exon 1 of 10	NP_695010.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A6	ENST00000360421.9	TSL:1 MANE Select	c.149G>A	p.Arg50His	missense	Exon 1 of 10	ENSP00000353597.4
	SLC22A6	ENST00000377871.7	TSL:1	c.149G>A	p.Arg50His	missense	Exon 1 of 10	ENSP00000367102.3
	SLC22A6	ENST00000421062.2	TSL:1	c.149G>A	p.Arg50His	missense	Exon 1 of 10	ENSP00000404441.2

Frequencies

GnomAD3 genomes AF: 0.0185 AC: 2821 AN: 152106 Hom.: 84 Cov.: 32

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0167

GnomAD2 exomes AF: 0.00487 AC: 1202 AN: 246760 AF XY: 0.00355

Gnomad AFR exome AF: 0.0680

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000172

Gnomad OTH exome AF: 0.00297

GnomAD4 exome AF: 0.00200 AC: 2929 AN: 1461366 Hom.: 78 Cov.: 33 AF XY: 0.00172 AC XY: 1247 AN XY: 726980

African (AFR) AF: 0.0680 AC: 2277 AN: 33476

American (AMR) AF: 0.00311 AC: 139 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39692

South Asian (SAS) AF: 0.000128 AC: 11 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53202

Middle Eastern (MID) AF: 0.00312 AC: 18 AN: 5766

European-Non Finnish (NFE) AF: 0.000225 AC: 250 AN: 1111820

Other (OTH) AF: 0.00383 AC: 231 AN: 60350

GnomAD4 genome AF: 0.0186 AC: 2831 AN: 152224 Hom.: 84 Cov.: 32 AF XY: 0.0181 AC XY: 1347 AN XY: 74424

African (AFR) AF: 0.0645 AC: 2677 AN: 41532

American (AMR) AF: 0.00654 AC: 100 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 67996

Other (OTH) AF: 0.0166 AC: 35 AN: 2114

Alfa AF: 0.00543 Hom.: 64

Bravo AF: 0.0213

ESP6500AA AF: 0.0654 AC: 288

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00583 AC: 708

Asia WGS AF: 0.00433 AC: 16 AN: 3478

EpiCase AF: 0.000382

EpiControl AF: 0.000712

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Benign	-0.43
Eigen_PC	Benign	-0.46
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.65	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		0.98
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.11
Sift	Uncertain	0.024	D
Sift4G	Benign	0.18	T
Polyphen		0.38	B
Vest4		0.12
MVP		0.59
MPC		0.69
ClinPred		0.019	T
GERP RS		2.8
PromoterAI		0.0028	Neutral
Varity_R		0.085
gMVP		0.48
Mutation Taster		=100/0	polymorphism (auto)

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: rs11568626; hg19: chr11-62752014;