Genetic Variant NM_007163.4:c.292C>A (chr18-45625824-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_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. 16/22 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0650

Publications

1 publications found

Variant links:

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]

SLC14A2 links:

ENSG00000287943 (HGNC:):

ENSG00000287943 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061927557).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC14A2	NM_007163.4	MANE Select	c.292C>A	p.Leu98Ile	missense	Exon 3 of 20	NP_009094.3
SLC14A2	NM_001242692.2		c.292C>A	p.Leu98Ile	missense	Exon 4 of 21	NP_001229621.1	Q15849-1
SLC14A2	NM_001371319.1		c.292C>A	p.Leu98Ile	missense	Exon 7 of 24	NP_001358248.1	Q15849-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SLC14A2	ENST00000255226.11	TSL:1 MANE Select	c.292C>A	p.Leu98Ile	missense	Exon 3 of 20	ENSP00000255226.5	Q15849-1
SLC14A2	ENST00000586448.5	TSL:2	c.292C>A	p.Leu98Ile	missense	Exon 4 of 21	ENSP00000465953.1	Q15849-1
SLC14A2	ENST00000323329.3	TSL:2	n.292C>A		non_coding_transcript_exon	Exon 3 of 11	ENSP00000320689.3	E7EPU1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000568

AC:

AN:

175970

AF XY:

0.00

show subpopulations

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 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:

AN:

1356920

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

668854

African (AFR)

AF:

0.00

AC:

AN:

27316

American (AMR)

AF:

0.00

AC:

AN:

24884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23136

East Asian (EAS)

AF:

0.00

AC:

AN:

33130

South Asian (SAS)

AF:

0.00

AC:

AN:

69346

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5456

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1065352

Other (OTH)

AF:

0.00

AC:

AN:

55910

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.4

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.16

Eigen

Benign

-0.72

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.47

M_CAP

Benign

0.0073

MetaRNN

Benign

0.062

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

PhyloP100

0.065

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.020

REVEL

Benign

0.017

Sift

Benign

0.59

Sift4G

Benign

0.33

Polyphen

0.0010

Vest4

0.21

MutPred

0.24

Gain of catalytic residue at L98 (P = 0.0067)

MVP

0.26

MPC

0.070

ClinPred

0.10

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over