chr18-45625690-G-T

Variant names:

• chr18-45625690-G-T
• rs145237117
• NM_007163.4:c.158G>T

Variant summary

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

The NM_007163.4(SLC14A2):​c.158G>T​(p.Arg53Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,392,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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. R53Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: SLC14A2 NM_007163.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.67
• 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]

ENSG00000287943 (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.158G>T	p.Arg53Leu	missense	Exon 3 of 20	NP_009094.3
	SLC14A2	NM_001242692.2		c.158G>T	p.Arg53Leu	missense	Exon 4 of 21	NP_001229621.1	Q15849-1
	SLC14A2	NM_001371319.1		c.158G>T	p.Arg53Leu	missense	Exon 7 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.158G>T	p.Arg53Leu	missense	Exon 3 of 20	ENSP00000255226.5	Q15849-1
	SLC14A2	ENST00000586448.5	TSL:2	c.158G>T	p.Arg53Leu	missense	Exon 4 of 21	ENSP00000465953.1	Q15849-1
	SLC14A2	ENST00000323329.3	TSL:2	n.158G>T		non_coding_transcript_exon	Exon 3 of 11	ENSP00000320689.3	E7EPU1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.18e-7 AC: 1 AN: 1392560 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 689520

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 29110

American (AMR) AF: 0.00 AC: 0 AN: 31366

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24478

East Asian (EAS) AF: 0.00 AC: 0 AN: 34528

South Asian (SAS) AF: 0.00 AC: 0 AN: 73386

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52870

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5608

European-Non Finnish (NFE) AF: 9.23e-7 AC: 1 AN: 1083498

Other (OTH) AF: 0.00 AC: 0 AN: 57716

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.24
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Uncertain	0.80	D
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.46	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.7
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.23
Sift	Benign	0.031	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.52
MutPred		0.13		Loss of methylation at K50 (P = 0.0881)
MVP		0.48
MPC		0.083
ClinPred		0.90	D
GERP RS		4.9
Varity_R		0.11
gMVP		0.44
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.23		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.23		Position offset: 15

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

Other links and lift over

dbSNP: rs145237117; hg19: chr18-43205655;