3-38307600-C-G

Position:

• chr3-38307600-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001320033.2(SLC22A14):​c.655C>G​(p.Leu219Val) 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. L219L) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC22A14 NM_001320033.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.968

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=0.23922086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A14	NM_001320033.2	c.655C>G	p.Leu219Val	missense_variant	4/11	ENST00000448498.6	NP_001306962.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A14	ENST00000448498.6	c.655C>G	p.Leu219Val	missense_variant	4/11	1	NM_001320033.2	ENSP00000396283.1
SLC22A14	ENST00000273173.4	c.655C>G	p.Leu219Val	missense_variant	3/10	1		ENSP00000273173.4
SLC22A14	ENST00000466887.5	c.259C>G	p.Leu87Val	missense_variant	4/4	4		ENSP00000442528.1
SLC22A14	ENST00000496724.1	n.1716C>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

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

Jun 24, 2022

The c.655C>G (p.L219V) alteration is located in exon 3 (coding exon 3) of the SLC22A14 gene. This alteration results from a C to G substitution at nucleotide position 655, causing the leucine (L) at amino acid position 219 to be replaced by a valine (V). 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	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	12
DANN	Benign	0.93
DEOGEN2	Benign	0.14	.;T;T
Eigen	Benign	-0.73
Eigen_PC	Benign	-0.80
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.63	T;.;T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.24	T;T;T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.6	.;L;L
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.8	D;D;D
REVEL	Benign	0.13
Sift	Uncertain	0.0060	D;D;D
Sift4G	Benign	0.16	T;D;D
Polyphen		0.29	.;B;B
Vest4		0.084, 0.090
MutPred		0.67		.;Loss of stability (P = 0.0906);Loss of stability (P = 0.0906);
MVP		0.27
MPC		0.35
ClinPred		0.60	D
GERP RS		-0.27
Varity_R		0.27
gMVP		0.22

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139716522; hg19: chr3-38349091;