18-45672918-G-T

Position:

• chr18-45672918-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_007163.4(SLC14A2):​c.2248G>T​(p.Val750Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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. V750I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC14A2 NM_007163.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.01

Genes affected

SLC14A2 (HGNC:10919): (solute carrier family 14 member 2) The protein encoded by this gene belongs to the urea transporter family. In mammalian cells, urea is the chief end product of nitrogen catabolism, and plays an important role in the urinary concentration mechanism. This protein is expressed in the inner medulla of the kidney, and mediates rapid transepithelial urea transport across the inner medullary collecting duct. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Sep 2011]

ENSG00000288545 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.798

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC14A2	NM_007163.4	c.2248G>T	p.Val750Phe	missense_variant	17/20	ENST00000255226.11	NP_009094.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC14A2	ENST00000255226.11	c.2248G>T	p.Val750Phe	missense_variant	17/20	1	NM_007163.4	ENSP00000255226.5
SLC14A2	ENST00000586448.5	c.2248G>T	p.Val750Phe	missense_variant	18/21	2		ENSP00000465953.1
ENSG00000288545	ENST00000589510.5	n.207-3445C>A		intron_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.36
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.010
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;T
Eigen	Uncertain	0.40
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Benign	0.079	D
MetaRNN	Pathogenic	0.80	D;D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Uncertain	2.8	M;M
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.3	.;D
REVEL	Uncertain	0.38
Sift	Uncertain	0.0040	.;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.95	P;P
Vest4		0.69
MutPred		0.47		Gain of helix (P = 0.0199);Gain of helix (P = 0.0199);
MVP		0.55
MPC		0.44
ClinPred		0.95	D
GERP RS		4.0
Varity_R		0.37
gMVP		0.96

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs1123617; hg19: chr18-43252883;