Variant chr4-25662723-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The NM_006424.3(SLC34A2):c.131C>G(p.Pro44Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000626 in 1,613,998 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

SLC34A2
NM_006424.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.13

Variant links:

Genes affected

SLC34A2 (HGNC:11020): (solute carrier family 34 member 2) The protein encoded by this gene is a pH-sensitive sodium-dependent phosphate transporter. Phosphate uptake is increased at lower pH. Defects in this gene are a cause of pulmonary alveolar microlithiasis. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, May 2010]

SLC34A2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024544388).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000408 (62/152106) while in subpopulation AFR AF= 0.00142 (59/41430). AF 95% confidence interval is 0.00113. There are 0 homozygotes in gnomad4. There are 30 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SLC34A2	NM_006424.3 linkuse as main transcript	c.131C>G	p.Pro44Arg	missense_variant	3/13	ENST00000382051.8	NP_006415.3
SLC34A2	NM_001177998.2 linkuse as main transcript	c.128C>G	p.Pro43Arg	missense_variant	3/13		NP_001171469.2
SLC34A2	NM_001177999.2 linkuse as main transcript	c.128C>G	p.Pro43Arg	missense_variant	3/13		NP_001171470.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC34A2	ENST00000382051.8 linkuse as main transcript	c.131C>G	p.Pro44Arg	missense_variant	3/13	1	NM_006424.3	ENSP00000371483	P4	O95436-1

Frequencies

GnomAD3 genomes

AF:

0.000408

AC:

AN:

152106

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00142

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000915

AC:

AN:

251468

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00135

Gnomad AMR exome

AF:

0.0000289

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

AF:

0.0000267

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000408

AC:

AN:

152106

Hom.:

Cov.:

AF XY:

0.000404

AC XY:

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.00142

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.0000792

Hom.:

Bravo

AF:

0.000423

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000741

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 14, 2021

The c.131C>G (p.P44R) alteration is located in exon 3 (coding exon 2) of the SLC34A2 gene. This alteration results from a C to G substitution at nucleotide position 131, causing the proline (P) at amino acid position 44 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.75

DEOGEN2

Benign

0.20

.;.;.;T;.;.

Eigen

Benign

-0.34

Eigen_PC

Benign

-0.36

FATHMM_MKL

Benign

0.40

LIST_S2

Benign

0.68

.;T;.;T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.025

T;T;T;T;T;T

MetaSVM

Benign

-0.88

MutationAssessor

Uncertain

2.4

.;.;.;M;.;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Uncertain

-3.6

.;D;N;N;N;D

REVEL

Benign

0.075

Sift

Benign

0.18

.;T;T;T;T;T

Sift4G

Uncertain

0.033

.;D;T;T;T;T

Polyphen

0.22

B;.;B;B;B;.

Vest4

0.17, 0.19, 0.17

MVP

0.61

MPC

0.27

ClinPred

0.060

GERP RS

5.5

Varity_R

0.040

gMVP

0.33

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over