11-62984542-C-T

Position:

• chr11-62984542-C-T

Variant summary

Our verdict is Benign. Variant got -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. 13/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• 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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A6	NM_153276.3	c.149G>A	p.Arg50His	missense_variant	1/10	ENST00000360421.9	NP_695008.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A6	ENST00000360421.9	c.149G>A	p.Arg50His	missense_variant	1/10	1	NM_153276.3	ENSP00000353597.4

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

GnomAD3 exomes AF: 0.00487 AC: 1202 AN: 246760 Hom.: 44 AF XY: 0.00355 AC XY: 476 AN XY: 133904

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 SAS exome AF: 0.000131

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

Gnomad4 AFR exome AF: 0.0680

Gnomad4 AMR exome AF: 0.00311

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000756

Gnomad4 SAS exome AF: 0.000128

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000225

Gnomad4 OTH exome AF: 0.00383

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

Gnomad4 AFR AF: 0.0645

Gnomad4 AMR AF: 0.00654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.00179 Hom.: 7

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 v4.3

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;T;T;T
MetaRNN	Benign	0.0030	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M;M;M;M
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.9	N;N;N;N
REVEL	Benign	0.11
Sift	Uncertain	0.024	D;D;T;D
Sift4G	Benign	0.18	T;T;T;T
Polyphen		0.38	B;B;B;B
Vest4		0.12
MVP		0.59
MPC		0.69
ClinPred		0.019	T
GERP RS		2.8
Varity_R		0.085
gMVP		0.48

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: rs11568626; hg19: chr11-62752014;