chr11-62977318-C-T

Variant names:

• chr11-62977318-C-T
• rs1239443098
• NM_153276.3:c.1431G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_153276.3(SLC22A6):​c.1431G>A​(p.Met477Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,954 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: SLC22A6 NM_153276.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16
• Publications: 1 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12003094).

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.1431G>A	p.Met477Ile	missense	Exon 9 of 10	NP_695008.1	Q4U2R8-2
	SLC22A6	NM_004790.5		c.1431G>A	p.Met477Ile	missense	Exon 9 of 10	NP_004781.2
	SLC22A6	NM_153278.3		c.1362-63G>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.1431G>A	p.Met477Ile	missense	Exon 9 of 10	ENSP00000353597.4	Q4U2R8-2
	SLC22A6	ENST00000377871.7	TSL:1	c.1431G>A	p.Met477Ile	missense	Exon 9 of 10	ENSP00000367102.3	Q4U2R8-1
	SLC22A6	ENST00000421062.2	TSL:1	c.1362-63G>A		intron	N/A	ENSP00000404441.2	Q4U2R8-4

Frequencies

GnomAD3 genomes AF: 0.00000660 AC: 1 AN: 151440 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 250774 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461514 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727080

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53070

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1112000

Other (OTH) AF: 0.00 AC: 0 AN: 60390

GnomAD4 genome AF: 0.00000660 AC: 1 AN: 151440 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 73964

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 41150

American (AMR) AF: 0.00 AC: 0 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5122

South Asian (SAS) AF: 0.00 AC: 0 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67792

Other (OTH) AF: 0.00 AC: 0 AN: 2082

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	20
DANN	Benign	0.47
DEOGEN2	Benign	0.10	T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.59	T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.33	N
PhyloP100		1.2
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.010	N
REVEL	Benign	0.16
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.024	B
Vest4		0.16
MutPred		0.63		Gain of glycosylation at S476 (P = 0.0665)
MVP		0.65
MPC		0.34
ClinPred		0.20	T
GERP RS		3.8
BranchPoint Hunter		0.0
Varity_R		0.39
gMVP		0.50
Mutation Taster		=88/12	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: rs1239443098; hg19: chr11-62744790; COSMIC: COSV64560124; COSMIC: COSV64560124;