Genetic Variant NM_007163.4:c.1529G>C (chr18-45666191-G-C) – 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.1529G>C(p.Arg510Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,306 control chromosomes in the GnomAD database, with no homozygous occurrence. 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.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC14A2
NM_007163.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.755

Publications

0 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=0.028582782).

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
SLC14A2	NM_007163.4	MANE Select	c.1529G>C	p.Arg510Pro	missense	Exon 12 of 20	NP_009094.3
SLC14A2	NM_001242692.2		c.1529G>C	p.Arg510Pro	missense	Exon 13 of 21	NP_001229621.1
SLC14A2	NM_001371319.1		c.1529G>C	p.Arg510Pro	missense	Exon 16 of 24	NP_001358248.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SLC14A2	ENST00000255226.11	TSL:1 MANE Select	c.1529G>C	p.Arg510Pro	missense	Exon 12 of 20	ENSP00000255226.5
SLC14A2	ENST00000586448.5	TSL:2	c.1529G>C	p.Arg510Pro	missense	Exon 13 of 21	ENSP00000465953.1
ENSG00000287943	ENST00000729208.1		n.228+22558C>G		intron	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461306

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726984

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1111478

Other (OTH)

AF:

0.00

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.44

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.16

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.0058

M_CAP

Benign

0.0034

MetaRNN

Benign

0.029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.2

PhyloP100

-0.76

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.70

REVEL

Benign

0.047

Sift

Benign

0.34

Sift4G

Benign

0.26

Polyphen

0.0

Vest4

0.092

MutPred

0.23

Gain of glycosylation at R510 (P = 0.0323)

MVP

0.030

MPC

0.092

ClinPred

0.091

GERP RS

-12

Varity_R

0.094

gMVP

0.50

Mutation Taster

=98/2

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over