3-38306349-C-T

Variant names:

• chr3-38306349-C-T
• rs9847584
• NM_001320033.2:c.323C>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001320033.2(SLC22A14):​c.323C>T​(p.Pro108Leu) 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 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P108H) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SLC22A14 NM_001320033.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.95
• Publications: 6 publications found

Genes affected

SLC22A14 (HGNC:8495): (solute carrier family 22 member 14) This gene encodes a member of the organic-cation transporter family. It is located in a gene cluster with another member of the family, organic cation transporter like 3. The encoded protein is a transmembrane protein which is thought to transport small molecules and since this protein is conserved among several species, it is suggested to have a fundamental role in mammalian systems. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32039657).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001320033.2. 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
	SLC22A14	NM_001320033.2	MANE Select	c.323C>T	p.Pro108Leu	missense	Exon 2 of 11	NP_001306962.1	Q9Y267
	SLC22A14	NM_004803.4		c.323C>T	p.Pro108Leu	missense	Exon 1 of 10	NP_004794.2	Q9Y267

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A14	ENST00000448498.6	TSL:1 MANE Select	c.323C>T	p.Pro108Leu	missense	Exon 2 of 11	ENSP00000396283.1	Q9Y267
	SLC22A14	ENST00000273173.4	TSL:1	c.323C>T	p.Pro108Leu	missense	Exon 1 of 10	ENSP00000273173.4	Q9Y267
	SLC22A14	ENST00000466887.5	TSL:4	c.-74C>T		5_prime_UTR	Exon 2 of 4	ENSP00000442528.1	F5H7H1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251474 AF XY: 0.00000736

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: 6.84e-7 AC: 1 AN: 1461882 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727244

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: 39696

South Asian (SAS) AF: 0.0000116 AC: 1 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: 0.00 AC: 0 AN: 1112004

Other (OTH) AF: 0.00 AC: 0 AN: 60396

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Benign	0.96
DEOGEN2	Benign	0.025	T
Eigen	Benign	0.065
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.32	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.9
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-4.5	D
REVEL	Benign	0.25
Sift	Benign	1.0	T
Sift4G	Uncertain	0.039	D
Polyphen		0.95	P
Vest4		0.14
MutPred		0.53		Gain of catalytic residue at P108 (P = 0.0039)
MVP		0.50
MPC		0.55
ClinPred		0.78	D
GERP RS		4.7
PromoterAI		0.0028	Neutral
Varity_R		0.15
gMVP		0.52
Mutation Taster		=81/19	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: rs9847584; hg19: chr3-38347840;