chr18-45625824-C-A

Variant names:

• chr18-45625824-C-A
• rs148670019
• NM_007163.4:c.292C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007163.4(SLC14A2):​c.292C>A​(p.Leu98Ile) 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. 15/21 in silico tools predict 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. L98F) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC14A2 NM_007163.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

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]

LOC105372093 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061927557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC14A2	NM_007163.4	c.292C>A	p.Leu98Ile	missense_variant	Exon 3 of 20	ENST00000255226.11	NP_009094.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC14A2	ENST00000255226.11	c.292C>A	p.Leu98Ile	missense_variant	Exon 3 of 20	1	NM_007163.4	ENSP00000255226.5
SLC14A2	ENST00000586448.5	c.292C>A	p.Leu98Ile	missense_variant	Exon 4 of 21	2		ENSP00000465953.1
SLC14A2	ENST00000323329.3	n.292C>A		non_coding_transcript_exon_variant	Exon 3 of 11	2		ENSP00000320689.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000568 AC: 1 AN: 175970 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 97316

Gnomad AFR exome AF: 0.0000881

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1356920 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 668854

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
CADD	Benign	7.4
DANN	Benign	0.78
DEOGEN2	Benign	0.16	T;T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.60
FATHMM_MKL	Benign	0.47	N
M_CAP	Benign	0.0073	T
MetaRNN	Benign	0.062	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;L
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.020	.;N
REVEL	Benign	0.017
Sift	Benign	0.59	.;T
Sift4G	Benign	0.33	T;T
Polyphen		0.0010	B;B
Vest4		0.21
MutPred		0.24		Gain of catalytic residue at L98 (P = 0.0067);Gain of catalytic residue at L98 (P = 0.0067);
MVP		0.26
MPC		0.070
ClinPred		0.10	T
GERP RS		2.6
Varity_R		0.039
gMVP		0.13

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

Publications

LitVar

Other links and lift over

dbSNP: rs148670019; hg19: chr18-43205789;