3-38306240-C-T

Variant names:

• chr3-38306240-C-T
• NM_001320033.2:c.214C>T

Variant summary

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

The NM_001320033.2(SLC22A14):​c.214C>T​(p.Leu72Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SLC22A14 NM_001320033.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.33
• Publications: 0 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24969691).

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.214C>T	p.Leu72Phe	missense	Exon 2 of 11	NP_001306962.1	Q9Y267
	SLC22A14	NM_004803.4		c.214C>T	p.Leu72Phe	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.214C>T	p.Leu72Phe	missense	Exon 2 of 11	ENSP00000396283.1	Q9Y267
	SLC22A14	ENST00000273173.4	TSL:1	c.214C>T	p.Leu72Phe	missense	Exon 1 of 10	ENSP00000273173.4	Q9Y267
	SLC22A14	ENST00000466887.5	TSL:4	c.-119-64C>T		intron	N/A	ENSP00000442528.1	F5H7H1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

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	Benign	0.11
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.019	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.79	D
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.030	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.3
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.2	D
REVEL	Benign	0.13
Sift	Benign	0.041	D
Sift4G	Uncertain	0.026	D
Polyphen		0.97	D
Vest4		0.086
MutPred		0.42		Loss of stability (P = 0.1204)
MVP		0.41
MPC		0.58
ClinPred		0.96	D
GERP RS		2.8
PromoterAI		0.016	Neutral
Varity_R		0.13
gMVP		0.44
Mutation Taster		=80/20	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

hg19: chr3-38347731; COSMIC: COSV56199316; COSMIC: COSV56199316;