5-132313639-G-C

Variant names:

• chr5-132313639-G-C
• rs144031153
• NM_003059.3:c.523G>C

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_003059.3(SLC22A4):​c.523G>C​(p.Ala175Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. A175T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC22A4 NM_003059.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.560
• Publications: 0 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.769

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.523G>C	p.Ala175Pro	missense	Exon 3 of 10	NP_003050.2
	MIR3936HG	NR_110997.1		n.825-1386C>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.523G>C	p.Ala175Pro	missense	Exon 3 of 10	ENSP00000200652.3	Q9H015
	MIR3936HG	ENST00000621103.4	TSL:1	n.825-1386C>G		intron	N/A
	SLC22A4	ENST00000947750.1		c.523G>C	p.Ala175Pro	missense	Exon 3 of 10	ENSP00000617809.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461868 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 727234

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: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111988

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Uncertain	0.068	T
BayesDel_noAF	Benign	-0.14
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T
Eigen	Benign	-0.56
Eigen_PC	Benign	-0.74
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.82	T
M_CAP	Uncertain	0.097	D
MetaRNN	Pathogenic	0.77	D
MetaSVM	Benign	-0.52	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		0.56
PrimateAI	Benign	0.30	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.48
Sift	Benign	0.11	T
Sift4G	Benign	0.14	T
Polyphen		0.86	P
Vest4		0.69
MutPred		0.64		Loss of catalytic residue at A175 (P = 0.0068)
MVP		0.76
MPC		0.85
ClinPred		0.61	D
GERP RS		-1.2
Varity_R		0.81
gMVP		0.83
Mutation Taster		=92/8	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: rs144031153; hg19: chr5-131649332;