dbSNP rs1211258954: SLC14A2:p.Asp75Asn (chr18-45625755-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_007163.4(SLC14A2):c.223G>A(p.Asp75Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000707 in 1,413,568 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. D75Y) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SLC14A2
NM_007163.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.89

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10850388).

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.223G>A	p.Asp75Asn	missense	Exon 3 of 20	NP_009094.3
SLC14A2	NM_001242692.2		c.223G>A	p.Asp75Asn	missense	Exon 4 of 21	NP_001229621.1	Q15849-1
SLC14A2	NM_001371319.1		c.223G>A	p.Asp75Asn	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.223G>A	p.Asp75Asn	missense	Exon 3 of 20	ENSP00000255226.5	Q15849-1
SLC14A2	ENST00000586448.5	TSL:2	c.223G>A	p.Asp75Asn	missense	Exon 4 of 21	ENSP00000465953.1	Q15849-1
SLC14A2	ENST00000323329.3	TSL:2	n.223G>A		non_coding_transcript_exon	Exon 3 of 11	ENSP00000320689.3	E7EPU1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1413568

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

701690

show subpopulations

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

African (AFR)

AF:

0.0000332

AC:

AN:

30092

American (AMR)

AF:

0.00

AC:

AN:

35054

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24964

East Asian (EAS)

AF:

0.00

AC:

AN:

35838

South Asian (SAS)

AF:

0.00

AC:

AN:

77222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53016

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5664

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1093250

Other (OTH)

AF:

0.00

AC:

AN:

58468

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

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

0.10

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.84

M_CAP

Benign

0.0051

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

4.9

PrimateAI

Benign

0.33

PROVEAN

Benign

0.11

REVEL

Benign

0.10

Sift

Benign

0.20

Sift4G

Benign

0.094

Polyphen

0.22

Vest4

0.18

MutPred

0.19

Loss of ubiquitination at K72 (P = 0.0228)

MVP

0.19

MPC

0.070

ClinPred

0.79

GERP RS

6.0

Varity_R

0.13

gMVP

0.14

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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