chr3-38306240-C-T

Position:

• chr3-38306240-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 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

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]

SLC22A14 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A14	NM_001320033.2	c.214C>T	p.Leu72Phe	missense_variant	2/11	ENST00000448498.6	NP_001306962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A14	ENST00000448498.6	c.214C>T	p.Leu72Phe	missense_variant	2/11	1	NM_001320033.2	ENSP00000396283.1
SLC22A14	ENST00000273173.4	c.214C>T	p.Leu72Phe	missense_variant	1/10	1		ENSP00000273173.4
SLC22A14	ENST00000466887.5	c.-119-64C>T		intron_variant		4		ENSP00000442528.1
SLC22A14	ENST00000496724.1	n.1067C>T		non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 17, 2023

The c.214C>T (p.L72F) alteration is located in exon 1 (coding exon 1) of the SLC22A14 gene. This alteration results from a C to T substitution at nucleotide position 214, causing the leucine (L) at amino acid position 72 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

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;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;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.4	M;M
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-3.2	D;D
REVEL	Benign	0.13
Sift	Benign	0.041	D;D
Sift4G	Uncertain	0.026	D;D
Polyphen		0.97	D;D
Vest4		0.086
MutPred		0.42		Loss of stability (P = 0.1204);Loss of stability (P = 0.1204);
MVP		0.41
MPC		0.58
ClinPred		0.96	D
GERP RS		2.8
Varity_R		0.13
gMVP		0.44

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

Publications

No publications associated with this variant yet.

Other links and lift over

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