rs35008345

Variant names:

• chr11-64556141-C-T
• rs35008345
• NM_018484.4:c.142C>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_018484.4(SLC22A11):​c.142C>T​(p.Arg48*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0041 in 1,614,162 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: 𝑓 0.0027 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0042 (18 hom.)
• Consequence: SLC22A11 NM_018484.4 stop_gained
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.92
• Publications: 18 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: Likely_benign. The variant received -6 ACMG points.

• BP6: Variant 11-64556141-C-T is Benign according to our data. Variant chr11-64556141-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3038511.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 4 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A11	NM_018484.4	MANE Select	c.142C>T	p.Arg48*	stop_gained	Exon 1 of 10	NP_060954.1
	SLC22A11	NM_001307985.2		c.142C>T	p.Arg48*	stop_gained	Exon 1 of 8	NP_001294914.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A11	ENST00000301891.9	TSL:1 MANE Select	c.142C>T	p.Arg48*	stop_gained	Exon 1 of 10	ENSP00000301891.4
	SLC22A11	ENST00000377581.7	TSL:5	c.142C>T	p.Arg48*	stop_gained	Exon 1 of 9	ENSP00000366804.3
	SLC22A11	ENST00000377585.7	TSL:2	c.142C>T	p.Arg48*	stop_gained	Exon 1 of 8	ENSP00000366809.3

Frequencies

GnomAD3 genomes AF: 0.00267 AC: 407 AN: 152160 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.000700

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.0173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00415

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.00288 AC: 725 AN: 251470 AF XY: 0.00283

Gnomad AFR exome AF: 0.00123

Gnomad AMR exome AF: 0.00159

Gnomad ASJ exome AF: 0.0142

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00148

Gnomad NFE exome AF: 0.00392

Gnomad OTH exome AF: 0.00424

GnomAD4 exome AF: 0.00425 AC: 6211 AN: 1461884 Hom.: 18 Cov.: 31 AF XY: 0.00408 AC XY: 2966 AN XY: 727242

African (AFR) AF: 0.00102 AC: 34 AN: 33480

American (AMR) AF: 0.00161 AC: 72 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0132 AC: 344 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86258

European-Finnish (FIN) AF: 0.00191 AC: 102 AN: 53412

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5768

European-Non Finnish (NFE) AF: 0.00475 AC: 5281 AN: 1112010

Other (OTH) AF: 0.00596 AC: 360 AN: 60396

GnomAD4 genome AF: 0.00267 AC: 407 AN: 152278 Hom.: 4 Cov.: 32 AF XY: 0.00254 AC XY: 189 AN XY: 74460

African (AFR) AF: 0.000698 AC: 29 AN: 41556

American (AMR) AF: 0.00118 AC: 18 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0173 AC: 60 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00415 AC: 282 AN: 68010

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00365 Hom.: 5

Bravo AF: 0.00301

TwinsUK AF: 0.00566 AC: 21

ALSPAC AF: 0.00778 AC: 30

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00372 AC: 32

ExAC AF: 0.00260 AC: 316

Asia WGS AF: 0.000289 AC: 2 AN: 3478

EpiCase AF: 0.00382

EpiControl AF: 0.00504

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	SLC22A11-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	36
DANN	Uncertain	1.0
Eigen	Uncertain	0.35
Eigen_PC	Benign	0.093
FATHMM_MKL	Uncertain	0.83	D
PhyloP100		1.9
Vest4		0.80
GERP RS		2.9
PromoterAI		-0.051	Neutral
Mutation Taster		=178/22	disease causing (fs/PTC)

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: rs35008345; hg19: chr11-64323613; COSMIC: COSV99042481;