SLC22A6 p.Arg454Gln

Variant names:

• chr11-62977388-C-T
• NM_153276.3:c.1362-1G>A

Your query was ambiguous. Multiple possible variants found:

• chr11-62977388-C-T
• chr11-62977387-CC-TT

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_153276.3(SLC22A6):​c.1362-1G>A variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC22A6 NM_153276.3 splice_acceptor, intron
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.82
• Publications: 0 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: Likely_pathogenic. The variant received 6 ACMG points.

• PVS1: Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.123411976 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.
• PM2: Very rare variant in population databases, with high coverage

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A6	NM_153276.3	MANE Select	c.1362-1G>A		splice_acceptor intron	N/A	NP_695008.1	Q4U2R8-2
	SLC22A6	NM_004790.5		c.1362-1G>A		splice_acceptor intron	N/A	NP_004781.2
	SLC22A6	NM_153278.3		c.1362-133G>A		intron	N/A	NP_695010.1	Q4U2R8-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A6	ENST00000360421.9	TSL:1 MANE Select	c.1362-1G>A		splice_acceptor intron	N/A	ENSP00000353597.4	Q4U2R8-2
	SLC22A6	ENST00000377871.7	TSL:1	c.1362-1G>A		splice_acceptor intron	N/A	ENSP00000367102.3	Q4U2R8-1
	SLC22A6	ENST00000421062.2	TSL:1	c.1362-133G>A		intron	N/A	ENSP00000404441.2	Q4U2R8-4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.42	D
BayesDel_noAF	Pathogenic	0.37
CADD	Pathogenic	31
DANN	Uncertain	1.0
Eigen	Pathogenic	1.1
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	0.99	D
PhyloP100		7.8
Mutation Taster		=3/97	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.96
SpliceAI score (max)		0.76		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.76		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr11-62744860;