18-45682394-G-C

Variant names:

• chr18-45682394-G-C
• rs3745009
• NM_007163.4:c.2638G>C

Variant summary

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

The NM_007163.4(SLC14A2):​c.2638G>C​(p.Ala880Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SLC14A2 NM_007163.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.09
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007163.4. 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
	SLC14A2	NM_007163.4	MANE Select	c.2638G>C	p.Ala880Pro	missense	Exon 20 of 20	NP_009094.3
	SLC14A2	NM_001242692.2		c.2638G>C	p.Ala880Pro	missense	Exon 21 of 21	NP_001229621.1	Q15849-1
	SLC14A2	NM_001371319.1		c.2638G>C	p.Ala880Pro	missense	Exon 24 of 24	NP_001358248.1	Q15849-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC14A2	ENST00000255226.11	TSL:1 MANE Select	c.2638G>C	p.Ala880Pro	missense	Exon 20 of 20	ENSP00000255226.5	Q15849-1
	SLC14A2	ENST00000586448.5	TSL:2	c.2638G>C	p.Ala880Pro	missense	Exon 21 of 21	ENSP00000465953.1	Q15849-1
	ENSG00000288545	ENST00000589510.5	TSL:5	n.206+10001C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 46

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.44
BayesDel_addAF	Benign	-0.050	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.033	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		2.1
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.28
Sift	Benign	0.18	T
Sift4G	Benign	0.11	T
Polyphen		0.88	P
Vest4		0.29
MutPred		0.60		Gain of relative solvent accessibility (P = 0.0215)
MVP		0.41
MPC		0.44
ClinPred		0.94	D
GERP RS		5.1
Varity_R		0.53
gMVP		0.95

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs3745009; hg19: chr18-43262359;