NM_003059.3:c.917T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003059.3(SLC22A4):​c.917T>C​(p.Ile306Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.606 in 1,609,940 control chromosomes in the GnomAD database, including 302,378 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (30893 hom., cov: 32)
  • Exomes 𝑓: 0.60 (271485 hom.)
• Consequence: SLC22A4 NM_003059.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=2.2935872E-6).
• BP6: Variant 5-132327369-T-C is Benign according to our data. Variant chr5-132327369-T-C is described in ClinVar as Benign. ClinVar VariationId is 1270019.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

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>C	p.Ile306Thr	missense	Exon 5 of 10	NP_003050.2
	MIR3936HG	NR_110997.1		n.824+4820A>G		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>C	p.Ile306Thr	missense	Exon 5 of 10	ENSP00000200652.3	Q9H015
	MIR3936HG	ENST00000621103.4	TSL:1	n.824+4820A>G		intron	N/A
	SLC22A4	ENST00000947750.1		c.917T>C	p.Ile306Thr	missense	Exon 5 of 10	ENSP00000617809.1

Frequencies

GnomAD3 genomes AF: 0.629 AC: 95537 AN: 152006 Hom.: 30860 Cov.: 32

Gnomad AFR AF: 0.744

Gnomad AMI AF: 0.761

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.590

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.375

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.632

GnomAD2 exomes AF: 0.579 AC: 145387 AN: 251158 AF XY: 0.565

Gnomad AFR exome AF: 0.746

Gnomad AMR exome AF: 0.692

Gnomad ASJ exome AF: 0.602

Gnomad EAS exome AF: 0.375

Gnomad FIN exome AF: 0.496

Gnomad NFE exome AF: 0.619

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.604 AC: 880532 AN: 1457816 Hom.: 271485 Cov.: 33 AF XY: 0.596 AC XY: 432545 AN XY: 725412

African (AFR) AF: 0.747 AC: 24969 AN: 33408

American (AMR) AF: 0.684 AC: 30576 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.604 AC: 15760 AN: 26106

East Asian (EAS) AF: 0.344 AC: 13651 AN: 39658

South Asian (SAS) AF: 0.388 AC: 33451 AN: 86160

European-Finnish (FIN) AF: 0.500 AC: 26677 AN: 53384

Middle Eastern (MID) AF: 0.537 AC: 3092 AN: 5758

European-Non Finnish (NFE) AF: 0.628 AC: 696429 AN: 1108374

Other (OTH) AF: 0.596 AC: 35927 AN: 60262

GnomAD4 genome AF: 0.629 AC: 95625 AN: 152124 Hom.: 30893 Cov.: 32 AF XY: 0.618 AC XY: 45921 AN XY: 74356

African (AFR) AF: 0.744 AC: 30849 AN: 41488

American (AMR) AF: 0.659 AC: 10075 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.590 AC: 2049 AN: 3470

East Asian (EAS) AF: 0.351 AC: 1818 AN: 5184

South Asian (SAS) AF: 0.374 AC: 1804 AN: 4822

European-Finnish (FIN) AF: 0.495 AC: 5235 AN: 10572

Middle Eastern (MID) AF: 0.537 AC: 158 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41607 AN: 67990

Other (OTH) AF: 0.632 AC: 1336 AN: 2114

Alfa AF: 0.615 Hom.: 100470

Bravo AF: 0.653

TwinsUK AF: 0.643 AC: 2385

ALSPAC AF: 0.627 AC: 2416

ESP6500AA AF: 0.739 AC: 3256

ESP6500EA AF: 0.615 AC: 5291

ExAC AF: 0.576 AC: 69972

Asia WGS AF: 0.403 AC: 1402 AN: 3476

EpiCase AF: 0.622

EpiControl AF: 0.630

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	15
DANN	Benign	0.89
DEOGEN2	Benign	0.30	T
Eigen	Benign	-0.87
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.34	N
LIST_S2	Benign	0.70	T
MetaRNN	Benign	0.0000023	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.1	L
PhyloP100		2.3
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.14
Sift	Benign	0.046	D
Sift4G	Uncertain	0.035	D
Polyphen		0.0020	B
Vest4		0.026
MPC		0.29
ClinPred		0.015	T
GERP RS		-1.1
Varity_R		0.22
gMVP		0.36
Mutation Taster		=98/2	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: rs272893; hg19: chr5-131663062; COSMIC: COSV52358339; COSMIC: COSV52358339;