11-62998959-A-T

Variant names:

• chr11-62998959-A-T
• rs2276299
• NM_004254.4:c.723T>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_004254.4(SLC22A8):​c.723T>A​(p.Thr241Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,613,400 control chromosomes in the GnomAD database, including 25,912 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2219 hom., cov: 33)
  • Exomes 𝑓: 0.17 (23693 hom.)
• Consequence: SLC22A8 NM_004254.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.53
• Publications: 29 publications found

Genes affected

SLC22A8 (HGNC:10972): (solute carrier family 22 member 8) This gene encodes a protein 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 appears to be localized to the basolateral membrane of the kidney. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, May 2010]

ENSG00000301851 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-4.53 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004254.4. 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
	SLC22A8	NM_004254.4	MANE Select	c.723T>A	p.Thr241Thr	synonymous	Exon 5 of 11	NP_004245.2
	SLC22A8	NM_001184732.2		c.723T>A	p.Thr241Thr	synonymous	Exon 5 of 11	NP_001171661.1
	SLC22A8	NM_001184733.2		c.450T>A	p.Thr150Thr	synonymous	Exon 5 of 11	NP_001171662.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A8	ENST00000336232.7	TSL:1 MANE Select	c.723T>A	p.Thr241Thr	synonymous	Exon 5 of 11	ENSP00000337335.2
	SLC22A8	ENST00000430500.6	TSL:1	c.723T>A	p.Thr241Thr	synonymous	Exon 5 of 11	ENSP00000398548.2
	SLC22A8	ENST00000311438.12	TSL:1	c.723T>A	p.Thr241Thr	synonymous	Exon 4 of 9	ENSP00000311463.8

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23467 AN: 152164 Hom.: 2214 Cov.: 33

Gnomad AFR AF: 0.0624

Gnomad AMI AF: 0.0903

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.218

Gnomad EAS AF: 0.261

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.177

GnomAD2 exomes AF: 0.193 AC: 48385 AN: 251080 AF XY: 0.190

Gnomad AFR exome AF: 0.0609

Gnomad AMR exome AF: 0.344

Gnomad ASJ exome AF: 0.220

Gnomad EAS exome AF: 0.244

Gnomad FIN exome AF: 0.136

Gnomad NFE exome AF: 0.162

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.174 AC: 253864 AN: 1461118 Hom.: 23693 Cov.: 32 AF XY: 0.175 AC XY: 126861 AN XY: 726754

African (AFR) AF: 0.0538 AC: 1800 AN: 33480

American (AMR) AF: 0.347 AC: 15490 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 5788 AN: 26124

East Asian (EAS) AF: 0.266 AC: 10544 AN: 39676

South Asian (SAS) AF: 0.211 AC: 18175 AN: 86204

European-Finnish (FIN) AF: 0.134 AC: 7167 AN: 53408

Middle Eastern (MID) AF: 0.175 AC: 1012 AN: 5768

European-Non Finnish (NFE) AF: 0.165 AC: 182977 AN: 1111384

Other (OTH) AF: 0.181 AC: 10911 AN: 60372

GnomAD4 genome AF: 0.154 AC: 23481 AN: 152282 Hom.: 2219 Cov.: 33 AF XY: 0.157 AC XY: 11707 AN XY: 74450

African (AFR) AF: 0.0622 AC: 2585 AN: 41578

American (AMR) AF: 0.300 AC: 4589 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.218 AC: 756 AN: 3470

East Asian (EAS) AF: 0.261 AC: 1354 AN: 5184

South Asian (SAS) AF: 0.197 AC: 953 AN: 4828

European-Finnish (FIN) AF: 0.136 AC: 1439 AN: 10612

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11307 AN: 68016

Other (OTH) AF: 0.176 AC: 372 AN: 2112

Alfa AF: 0.160 Hom.: 1606

Bravo AF: 0.163

Asia WGS AF: 0.206 AC: 716 AN: 3478

EpiCase AF: 0.164

EpiControl AF: 0.168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.57
DANN	Benign	0.48
PhyloP100		-4.5
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: rs2276299; hg19: chr11-62766431; COSMIC: COSV60325283; COSMIC: COSV60325283;