NM_018484.4:c.463G>A

Variant names:

• chr11-64559204-G-A
• rs61744144
• NM_018484.4:c.463G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_018484.4(SLC22A11):​c.463G>A​(p.Val155Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00181 in 1,611,204 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 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 0.0081 (13 hom., cov: 31)
  • Exomes 𝑓: 0.0012 (25 hom.)
• Consequence: SLC22A11 NM_018484.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.187
• Publications: 5 publications found

Genes affected

SLC22A11 (HGNC:18120): (solute carrier family 22 member 11) The protein encoded by this gene is involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and is found mainly in the kidney and in the placenta, where it may act to prevent potentially harmful organic anions from reaching the fetus. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.013583392).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00805 (1225/152158) while in subpopulation AFR AF = 0.0265 (1098/41504). AF 95% confidence interval is 0.0252. There are 13 homozygotes in GnomAd4. There are 567 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 13 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018484.4. 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
	SLC22A11	NM_018484.4	MANE Select	c.463G>A	p.Val155Met	missense	Exon 2 of 10	NP_060954.1
	SLC22A11	NM_001307985.2		c.463G>A	p.Val155Met	missense	Exon 2 of 8	NP_001294914.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A11	ENST00000301891.9	TSL:1 MANE Select	c.463G>A	p.Val155Met	missense	Exon 2 of 10	ENSP00000301891.4
	SLC22A11	ENST00000377581.7	TSL:5	c.463G>A	p.Val155Met	missense	Exon 2 of 9	ENSP00000366804.3
	SLC22A11	ENST00000377585.7	TSL:2	c.463G>A	p.Val155Met	missense	Exon 2 of 8	ENSP00000366809.3

Frequencies

GnomAD3 genomes AF: 0.00800 AC: 1217 AN: 152040 Hom.: 13 Cov.: 31

Gnomad AFR AF: 0.0263

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.00224 AC: 559 AN: 249080 AF XY: 0.00156

Gnomad AFR exome AF: 0.0257

Gnomad AMR exome AF: 0.00207

Gnomad ASJ exome AF: 0.000101

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000365

Gnomad OTH exome AF: 0.00198

GnomAD4 exome AF: 0.00116 AC: 1692 AN: 1459046 Hom.: 25 Cov.: 31 AF XY: 0.00112 AC XY: 810 AN XY: 725540

African (AFR) AF: 0.0292 AC: 973 AN: 33354

American (AMR) AF: 0.00236 AC: 105 AN: 44538

Ashkenazi Jewish (ASJ) AF: 0.0000384 AC: 1 AN: 26036

East Asian (EAS) AF: 0.00 AC: 0 AN: 39436

South Asian (SAS) AF: 0.000616 AC: 53 AN: 86106

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.00747 AC: 43 AN: 5754

European-Non Finnish (NFE) AF: 0.000293 AC: 325 AN: 1110210

Other (OTH) AF: 0.00319 AC: 192 AN: 60230

GnomAD4 genome AF: 0.00805 AC: 1225 AN: 152158 Hom.: 13 Cov.: 31 AF XY: 0.00762 AC XY: 567 AN XY: 74366

African (AFR) AF: 0.0265 AC: 1098 AN: 41504

American (AMR) AF: 0.00477 AC: 73 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 67982

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00377 Hom.: 8

Bravo AF: 0.00932

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.000259 AC: 1

ESP6500AA AF: 0.0268 AC: 118

ESP6500EA AF: 0.000698 AC: 6

ExAC AF: 0.00266 AC: 323

Asia WGS AF: 0.00491 AC: 17 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	12
DANN	Uncertain	0.98
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.68	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.79	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.19
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.24
Sift	Benign	0.057	T
Sift4G	Uncertain	0.030	D
Polyphen		0.73	P
Vest4		0.13
MVP		0.70
MPC		0.40
ClinPred		0.0030	T
GERP RS		-1.4
Varity_R		0.048
gMVP		0.14
Mutation Taster		=100/0	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: rs61744144; hg19: chr11-64326676; COSMIC: COSV57254422; COSMIC: COSV57254422;