5-132327369-T-G

Variant names:

• chr5-132327369-T-G
• rs272893
• NM_003059.3:c.917T>G

Variant summary

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

The NM_003059.3(SLC22A4):​c.917T>G​(p.Ile306Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,008 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I306T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000012 (1 hom.)
• Consequence: SLC22A4 NM_003059.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.30
• Publications: 97 publications found

Genes affected

SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]

MIR3936HG (HGNC:40538): (MIR3936 host gene)

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=0.22253686).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003059.3. 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
	SLC22A4	NM_003059.3	MANE Select	c.917T>G	p.Ile306Arg	missense	Exon 5 of 10	NP_003050.2
	MIR3936HG	NR_110997.1		n.824+4820A>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A4	ENST00000200652.4	TSL:1 MANE Select	c.917T>G	p.Ile306Arg	missense	Exon 5 of 10	ENSP00000200652.3	Q9H015
	MIR3936HG	ENST00000621103.4	TSL:1	n.824+4820A>C		intron	N/A
	SLC22A4	ENST00000947750.1		c.917T>G	p.Ile306Arg	missense	Exon 5 of 10	ENSP00000617809.1

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152064 Hom.: 0 Cov.: 32

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251158 AF XY: 0.00000737

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

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: 0.0000123 AC: 18 AN: 1459944 Hom.: 1 Cov.: 33 AF XY: 0.0000124 AC XY: 9 AN XY: 726340

African (AFR) AF: 0.00 AC: 0 AN: 33438

American (AMR) AF: 0.00 AC: 0 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39668

South Asian (SAS) AF: 0.00 AC: 0 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53396

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000162 AC: 18 AN: 1110318

Other (OTH) AF: 0.00 AC: 0 AN: 60324

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152064 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74270

African (AFR) AF: 0.00 AC: 0 AN: 41382

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68006

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 100470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.067	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.51
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.52	D
LIST_S2	Benign	0.81	T
M_CAP	Uncertain	0.086	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	0.56	N
PhyloP100		2.3
PrimateAI	Benign	0.27	T
PROVEAN	Pathogenic	-6.0	D
REVEL	Benign	0.23
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.051	T
Polyphen		0.73	P
Vest4		0.23
MutPred		0.49		Gain of MoRF binding (P = 0.0166)
MVP		0.67
MPC		0.42
ClinPred		0.50	D
GERP RS		-1.1
Varity_R		0.57
gMVP		0.49
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs272893; hg19: chr5-131663062; COSMIC: COSV52359758; COSMIC: COSV52359758;